The
The artificial embryo growth medium in which the fertilized ovum is immersed
during culture contains mostly glucose, pyruvate and energy-providing
components. It is also possible to add amino acids, nucleotides, vitamins
and cholesterol to improve embryo growth and development. All in all, the
mediums aim to mimic the optimal reproductive environment for each
developmental stage (see Landecker, 2016 ).
However, the big pharmaceutical companies that provide the mediums do not share
all the details, such as add-ons or percentages of different chemical
ingredients in their products, despite pressure from medical practitioners.
For instance, according to our informants, the Nordic Fertility Society has
tried to force companies to reveal this information without success. The
medical staff we talked with told us that in the early days of clinical IVF
work, they had been able to make their own mediums as laboratory craftwork;
now they were dependent on standard mediums provided by large companies,
because EU regulations only permitted CE-tested and certified mediums, which
only big companies were able to produce.
As a result, the choice of a medium for one’s IVF laboratory is made without
full information.
We are dependent on the commercial growth mediums [rather than
being able to make them in-house]. The one thing I have always
wished for is that at some point the producers of the mediums
should be supervised, just like IVF medications are controlled.
They are not controlled. They still have these product secrets
about what gets added into the mediums. I really hope there will
be [a change] because we put embryos in them. And these firms
can add some preparation that will make more beautiful embryos,
embryos that develop faster. What are the long-term effects?
Overall, I think we should pay attention not so much to what
kind of results the clinic has, how many pregnancies we manage
to induce, but think more about the effects [of embryo culture
and IVF] on the individual’s health and the health of the
children and health later in life. This is something that has
always worried me personally. … What is being done when, for
instance, some growth hormone is added into some mediums. No one
knows what effects it has. And then it may be a commercial
secret, so we don’t even know what exactly is in them.
(embryologist 4, clinic C)
We are dependent on the commercial growth mediums [rather than
being able to make them in-house]. The one thing I have always
wished for is that at some point the producers of the mediums
should be supervised, just like IVF medications are controlled.
They are not controlled. They still have these product secrets
about what gets added into the mediums. I really hope there will
be [a change] because we put embryos in them. And these firms
can add some preparation that will make more beautiful embryos,
embryos that develop faster. What are the long-term effects?
Overall, I think we should pay attention not so much to what
kind of results the clinic has, how many pregnancies we manage
to induce, but think more about the effects [of embryo culture
and IVF] on the individual’s health and the health of the
children and health later in life. This is something that has
always worried me personally. … What is being done when, for
instance, some growth hormone is added into some mediums. No one
knows what effects it has. And then it may be a commercial
secret, so we don’t even know what exactly is in them.
(embryologist 4, clinic C)
This embryologist sees the fact that commercial establishments often do not
disclose the exact composition (see Landecker, 2016 ) of their
mediums as ethically dubious and as needing to be controlled in the way that
IVF medications are controlled. There is suspicion that pharmaceutical
companies add chemicals to the mediums to make the embryos morphologically
beautiful and enhance their developmental performance – to improve the
embryo vitality as assessed in the grading models that ultimately lead to
the choice of an embryo for transfer. There is concern about the
implications of this for the long-term health of embryos and children.
This concern seems legitimate, as can be seen from a story one embryologist
told us about a sudden decrease in successful IVFs at her clinic: ‘The
medium manufacturer had changed something. That was revealed, but first they
said they had made no changes, but then there came news from other places as
well that there have been problems. Then they confessed’ (embryologist 1,
clinic E). It seems that the absence of information from the pharmaceutical
industry, which is explained away in terms of market advantage, not only
hinders the possibility of producing and knowing embryonic human life, but
is also a liability for that life in vitro .
Embryologists are aware that culture mediums only partially and artificially
mimic uterine surroundings, turning optimization into an uncertain and risky
affair. In contrast to the historical institutional goal of neutralizing
variability and making environments inert, the medium is reconceptualized
from a mere adequate background condition to a constitutive factor in the
making and knowing of human life forms. This scientific approach to
epigenetics necessitates attention not just to the medium’s biomaterials as
interactive agents, but also to the social, cultural, economic and political
constitution of the material setting ( Alder, 2013 ; Landecker, 2016 :
149).
The industrial setting of culture mediums for IVF also means that individual
clinics and chains do not share knowledge about their materials and
practices for business reasons. This caused frustration among the
embryologists in our study: Everyone does [embryo culture] in their own different ways [refers
to clinics] and it annoys me enormously that in this business
results are not comparable, really. You just think that, oh, so
you are transferring that sort of an embryo, I wonder what it
would look like at our place [if we were to choose same embryo].
It is an established fact that embryos grow faster in some
growth mediums. If you think about that, when you examine some
other [embryo], it looks at this moment like that. Can you trust
anything? If everything has an effect, it makes you feel awful,
like this is not working. There is no absolute [truth] when the
reality is that it varies. … But then we think, shall we use a
different medium, but how do we know [how they work]? Based on
one medium we could say this is a good embryo and based on
another we could say this is too fast and this is bad.
(embryologist 2, clinic C)
Everyone does [embryo culture] in their own different ways [refers
to clinics] and it annoys me enormously that in this business
results are not comparable, really. You just think that, oh, so
you are transferring that sort of an embryo, I wonder what it
would look like at our place [if we were to choose same embryo].
It is an established fact that embryos grow faster in some
growth mediums. If you think about that, when you examine some
other [embryo], it looks at this moment like that. Can you trust
anything? If everything has an effect, it makes you feel awful,
like this is not working. There is no absolute [truth] when the
reality is that it varies. … But then we think, shall we use a
different medium, but how do we know [how they work]? Based on
one medium we could say this is a good embryo and based on
another we could say this is too fast and this is bad.
(embryologist 2, clinic C)
This embryologist is very aware that the embryos as known are the product of
the growth medium. This knowledge also has consequences: The embryos are
graded differently and different kinds of embryo are transferred into the
intended mothers’ wombs at different clinics. However, as with the large
pharmaceutical corporations, it is not in the local private clinics’ market
interest to share their data: They prefer to keep their best practice,
acquired through time-consuming laboratory tinkering and trial and error, to
themselves. There is economic value in knowledge that is not shared. In the
commercial industry setting, economic value wins out over the ethical value
of openness.
The valuable knowledge here is not just knowledge of the type of medium used,
but also local know-how (see Levin and Leonelli, 2017 ).
Making a standard medium work is not automatic. Rather, it is an
accomplishment arrived at in the laboratory through careful, non-standard
craftwork. The embryologists in our study seemed reluctant to change the
medium brand they were using, which they had found to work
by doing and experiencing laboratory work.
We don’t change them often. We start using [new mediums] if … it is
more usable, like easier to use. (embryologist 1, clinic E) Sometimes we test new mediums from a different company. Usually I
think there is no difference. These tools are often [chosen]
according to what fits your hand the best and which one helps
you work better [with the embryos]. (embryologist 2, clinic
D)
We don’t change them often. We start using [new mediums] if … it is
more usable, like easier to use. (embryologist 1, clinic E)
Sometimes we test new mediums from a different company. Usually I
think there is no difference. These tools are often [chosen]
according to what fits your hand the best and which one helps
you work better [with the embryos]. (embryologist 2, clinic
D)
The industrially produced (and not fully known) mediums are tested on embryos
to see how they work in practice, to see how the embryos adapt to them. Via
their own testing, the clinics achieve higher pregnancy rates and improve
the practicalities of everyday laboratory work. Making mediums work by
testing involves not just the context of production of the medium itself,
but also the individual clinic and its hands-on labor. However, in clinical
IVF settings, the professionals are not able to isolate the substances that
are necessary or harmful for continued life because the composition of the
mediums is not known. The professionals also don’t know the (probably)
innumerable empirical tinkerings and tests that take place in pharmaceutical
industry laboratories before a medium is released to market, even though
those tests are part of the co-constitution of future embryos, inseparable
from their in vitro milieu. As one embryologist summed up,
‘we just have to trust that they have been properly tested’ (embryologist 2,
clinic D).
For the same reason of non-disclosure, many embryologists prefer to choose all
their mediums from the same provider – the embryo growth medium, freezing
medium, thawing medium and so on – as if they will fit together better. For
pharmaceutical companies, this purchasing logic means that selling one
medium equals selling a whole product line.
We choose the manufacturers according to experience and then we
prefer to take all of the mediums from the same manufacturer
because they work together well …. It is difficult to change
them because they have different substances in them and we want
the whole family then, so to speak. (embryologist 4, clinic
C)
We choose the manufacturers according to experience and then we
prefer to take all of the mediums from the same manufacturer
because they work together well …. It is difficult to change
them because they have different substances in them and we want
the whole family then, so to speak. (embryologist 4, clinic
C)
One might easily think that standard medium products bought from big
transnational pharmaceutical providers would make business easier for local
clinics, as they would not have to invest time and resources in making their
own mediums. Although it may take a period of careful craftwork to get
purchased mediums to work with the embryos, the clinics should be able to
stick with the same products for a long time thereafter, without having to
repeat the process. This industrial logic of cost-effectiveness is certainly
something the big pharmaceutical companies promote. However, in some
respects, both economic and ethical value gets lost in these forced dealings
with pharmaceutical corporations, since information on embryo epigenetics is
not shared.
It is no surprise, then, that when talking about mediums with the professionals
today, they bring into the conversations the early days of maverick small
businesses, when they used to craft their own. Such practice appears as a
(politically) more desirable practice, with a different distribution of
knowledge.
Data
To incorporate various laboratory knowledge production practices across
different locations, we use multi-sited ethnography ( Falzon, 2009 ; Hine, 2007 ).
Multi-sited ethnography recognizes that the research’s matter of concern is
constantly crafted in a range of locations and practices, including
laboratories, doctors’ offices, intended parents’ private reproductive
voyages and peer support groups. An ethnographic time frame is needed to
deal with the entire trajectories of embryo culture.
The article is based on two multi-sited ethnographic studies conducted at a
total of eight different private fertility clinics in Finland during
2013–2017, with a follow-up study from autumn 2019 onward. Both of our
larger research projects are concerned with the constitution of social
relations and selves in clinical reproductive healthcare practices in the
context of healthcare marketization. The fieldwork sites encompass fertility
clinic spaces including IVF laboratories, conferences and events and peer
support groups for intended parents. During our fieldwork periods, there
were between ten and fourteen commercial fertility clinics in Finland in
total. The combination of our data not only allows us to analyze material
from eight of those commercial clinics, but also to observe the links,
variations and tensions among practices that would not have been visible in
our respective separate data sets.
As is common in ethnographic enquiry, we repeatedly reframed our analysis of
our material through new knowledge produced collaboratively with
participants in the field ( Hammersley and Atkinson, 1995 ;
Holmes and
Marcus, 2008 ). This enabled us to examine how knowledge
practices are realized and challenged in specific, situational, everyday
clinical work. It also enabled us to see the political work involved in
normalizing technologies and in contesting, reformulating and reinforcing
technological practices and the market.
Altogether, the data collected in the two larger studies during 2013–2017 and
in the follow-up study that started in autumn 2019, comprises ethnographic
observations and video recordings (105 videos of appointments and
procedures) from six private fertility clinics (clinics A, B, C, D, E, and
F) and 27 in-depth interviews with medical personnel in seven clinics (eight
clinics participated in total). The videotapes analyzed in-depth in this
article comprise recordings of 42 procedures with embryologists in the
operating theater and five videos where embryologists are showing and
explaining the development of patients’ embryos to them via TLS. The
interviews analyzed comprise nine interviews with embryologists and six with
doctors, as they are the ones in charge of laboratory work in different
ways. The fieldwork was conducted in periods lasting between a few days and
two weeks alongside an intense period of participant observation at one
laboratory for one month. Additionally, the fieldwork included participant
observation at five Finnish and international conferences for
medical/laboratory staff, five public events that brought together various
stakeholders on (in)fertility issues and two information/recruitment events
for potential egg donors organized by private clinics. We also collected
documentary material, such as legislative and regulatory documents, care and
laboratory protocols and guidelines and hand-outs distributed to intended
parents.
Although this article focuses on observations and interviews conducted with
specific medical staff in clinics, we also draw on data gathered from
observations conducted over seven months in four peer support groups for
people experiencing involuntary childlessness, where necessary. A Finnish
infertility association organized these groups. Thirteen interviews with
intended parents were also conducted.
All interviewees and participants in video recordings signed an informed
consent form. Other participants gave oral consent to participate or were
informed beforehand of the presence of the researcher and given an
opportunity to object or withdraw from the event. At public events and
conferences, the researchers informed the organizers of the study
beforehand.
Practices
Theoretically, our article draws on the STS insight that knowledge both
describes and constitutes its objects (e.g. Jasanoff, 2004 ; Knorr-Cetina,
1981 ; Latour and Woolgar, 1986 ). Accordingly, we conceptualize
embryo culture as ways of knowing about embryonic life and viability. We aim
to explore technological processes and practices of knowledge production and
how they produce (what is perceived to be) legitimate and plausible
knowledge about embryos and their viability.
Knowledge production in the laboratory is generally seen as ‘through and
through relational, embodied, affective and practical’ craftwork ( Meskus, 2018 :
108). It is work that involves a multitude of actors, local and global,
human and non-human. In IVF laboratories those actors include technologies,
standards, embryologists, other clinical staff, intended parents, national
and supranational laws and regulations on the medical use of human tissues
and cells, the industrial players and the living biomaterial itself (see
Helosvuori,
2019 ). It is hands-on work, but ‘there can be no separation of
the hands-on and the intellectual reshaping of what cells are [and] what
they can do’ ( Landecker, 2007 : 26), as shown by pioneering laboratory
studies (e.g. Knorr-Cetina, 1981 ; Latour and Woolgar, 1986 ; Lynch, 1985 ). As
Sennett
(2008) describes, craft is characterized by affective and
attentive engagement with its object material to fulfill ‘the desire to do a
job well for its own sake’.
However, craftwork is subject to increasing political and economic demands for
its transformation into more standardized and automated systems of knowledge
production, moving from small-scale craft-like surroundings to
industrialized settings – scaling up. While standards and protocols may be
more common in clinical work than in experimental research, they also become
appropriated for uses for which they were never imagined in their design
( Bowker and Star,
1999 ; de
Laet and Mol, 2000 ), used in reflexive rather than clear-cut
ways, worked around ( Timmermans, 2015 ), and tinkered with to make them
work ( de Laet and Mol, 2000 ; Timmermans and Epstein,
2010 ).
In this article, we introduce a response to standardization that does not rest
on hype, hope or excitement. Some clinics resist standardization by
reinstating aspects of the craft production of knowledge, in the process
sketching new political realities. This response has previously been
identified in work practices such as artisanal food production, the home
birth movement ( Rothman, 2016 ) and even research management ( Davies and Horst,
2015 ), but it has not been identified in laboratory work to
date.
STS approaches have historically been accused of being apolitical or siding
with the strong due to their inability to fully theorize how and to what
ends materials link to the capitalist mode of production or institutional
power relations (e.g. Braunmühl, 2018 ; Law, 2004 : 13–14; Mol and Mesman,
1996 ; Rekret, 2018 ). It can be argued, however, that STS approaches
to knowledge production and its methods provide the tools to attend to
‘goodness’ in various activities: caring for many participants
simultaneously including oneself (see Davies and Horst, 2015 ; Homanen, 2019 ;
Lemke,
2018 : 45; Mol, 2008 ) and encompassing all participants’ economic
conditions. This caring exists alongside the logics and interests of
economic value accumulation and instrumentalization.
Conclusion
In this article, we have explored embryo culture in clinical IVF laboratories
as a knowledge production practice and process that ultimately aims to know
and select the most viable embryos for transfer. We have discussed the ways
in which incubator technologies (with and without TLS add-ons) and embryo
culture mediums enable and disable knowledge about embryo morphology,
embryogenesis and epigenetics. Our results regarding knowledge production
are a contribution to discussions of craftwork and standardization in
bioindustrialisation, which have hitherto mostly been discussed in the
context of research laboratories rather than clinical laboratories (however,
see e.g. Pavone and
Arias, 2012 ; Van de Wiel, 2019 ).
Prior research suggests that transnational pharmaceutical and biotechnological
giants rule the market for the commercialized products used in IVF; they
also aggressively promote standardization and automation in clinics ( Franklin, 2013 ;
Global Fertility
Alliance, 2018 ; Van de Wiel, 2019 ).
Standardization and automation can be also seen as requiring clinics to
scale up and branch out into new areas, geographically and otherwise ( Franklin, 2013 ;
see also Meskus,
2018 ). Despite this interest in capitalizing on the expanding
fertility market and life science-led expansions more broadly, automation
and standardization are only possible up to a point. This means that the
future of bioindustrialization depends on the successful financializaton and
commercialization of a mixture of human effort (patients and medics, in our
case), standards, machinery and the labor of living cells, as Franklin (2013)
points out. Our study offers a novel view into a few such possible mixtures
in IVF laboratories.
Our study confirms previous findings ( Foley and Whitaker, 2012 ; Muniesa et al.,
2017 ; Petersen and Krisjansen, 2015 ) that there is a persistent gap
between the enthusiastic market expectations and fuss around new
biotechnologies and their actual industrial success, including those in
clinical laboratories. TLS is a good example of this. While it is celebrated
as a revolutionary technology that makes an epistemic break in the practices
of knowing embryo viability by enabling staff to predict development times
(see also Van de Wiel,
2018 , 2019 ), TLS turns out to be not so practical in clinical
practice after all, or gets used in non-standard and non-automated craft
ways. This is not just because of the uncertainties and unpredictabilities
of the performance of living material, but also because local economic
interests do not always coincide with the larger industrial interests in
automation and do not exclude concern over patients’ finances.
Furthermore, while it is perhaps interesting for research, much of the detailed
knowledge about morphological features and embryogenesis enabled by TLS
seems to make no difference in clinical work and the predictive component –
which is based on algorithmic analyses of historical data sets and ideally
allows the automation of knowledge production – is regarded as unnecessary
and lacking. The craft of embryo culture also has value in itself: The
valued goal is to keep embryos perceived as optimal for transfer alive and
well in vitro until the blastocyst phase.
The second technology of much embryo culture – embryo culture mediums – enables
and enacts knowledge about not just embryogenesis, but also epigenetics.
However, because of supranational and national safety requirements,
pharmaceutical giants have a monopoly over the mediums’ distribution and
they refuse to share information about their composition. This is not
uncommon in commercial settings ( Landecker, 2007 , 2016 ). In order
to ‘get the job done’, clinicians simply need to trust the standards (see
Timmermans,
2015 : 80). However, professionals call for control from
regulators to force this information into the open in the name of liability
for human life.
Arguably, in our view, this lack of regulation results from the historical
understanding of mediums as mere uterine-like backgrounds, rather than as
co-constitutive artificial agents in embryo culture, which is how mediums
are perceived in epigenetics. This suggests that political attention to the
issue is needed. After all, the ultimate ‘product’ of the laboratory
practices in IVF is a human person and the practices might bear consequences
for following generations.
While commercial clinical establishments are not under the same pressure as
scientific research to share knowledge/data ( Birch, 2017 ; Levin and Leonelli,
2017 ), they are embedded in multiple exchanges and
expectations. Hilgartner (2012) has argued that data-sharing follows a
‘dialectic of revelation and concealment’ through which knowledge is
strategically made available and unavailable. In the case of IVF clinics,
what happens in a situation where there is no open information about
standard medium composition is that clinics make standard commercial mediums
work in their own laboratories, which involves bioassay experimentation with
embryos to see how they adapt to it. This experimentation is time-,
resource- and labor-intensive and involves and develops local know-how.
Thus, it comes as no surprise that the clinics, in turn, do not want to
share this valuable know-how with other clinics or the larger industry: It
is an achievement they want to capitalize on themselves. However, this
results in less knowledge about the mediums’ epigenetic effects, further
consolidating the bioindustry market, since embryologists feel that it is
risky not to buy a whole line of laboratory pharmaceutics from the same
provider.
The non-disclosure of milieu information, which affect embryonic life, causes
frustration among professionals, who feel responsible toward embryos, future
babies and intended parents. They are emotionally invested in the craftwork,
and as part of this, disclosure/non-disclosure involves ethical as well as
market value. Laboratory work is about both instrumentality and care, which,
as Meskus (2018)
argues, are mutually inclusive and interdependent when one seeks to make
biomaterial work in the ways hoped and planned in the age of
bioindustrialization (see also Adamson, 2010 ; Davies and Horst,
2015 ).
Can we then say that there are multiple bio-economies being drafted in clinical
practices, albeit not very explicitly all the time? These also include
bio-economies where mass production is not the ultimate goal – that is,
where the primary obstacles to automation and standardization are not
biological uniqueness, uncertainty or unpredictability. Rather, we are
talking about practices where craft kicks back. Such practices can also be
seen as models for reproductive care, drawing on a value system that
disdains the mass industrial approach.
Incubators
During our observations, IVF success was often reduced to the issue of embryo
quality in discussions at clinics and public events. First and foremost, the
incubator environments were seen as instrumental to ensuring the maintenance
of embryo quality and even to improving it. This was also discussed at peer
support group meetings. Patients wondered whether their clinics used the
best possible incubators, wanted to know about the expenses and whether they
could afford the incubator technologies.
The incubator technologies used at clinics during our fieldwork included a more
traditional incubator from which embryos were removed for assessment on a
daily basis, as well as a few different TLS (Vitrolife’s EmbryoScope and
Primo Vision, Auxogyn’s Eeva, and Esco Medical’s MIRI). The medical staff
believed that embryo quality could be improved with TLS because the
examination was conducted without removing the embryos from the incubator.
TLS do not otherwise improve embryo quality per se, although some research
(e.g. Chen et al.,
2013 ; Meseguer et al., 2012 ) suggests that TLS aid the selection of
the best-quality embryo for transfer because the embryos are ‘truly’ known
through this technology. Indeed, there is quite a lot of fuss about TLS in
both biomedical research and clinical practice. It has been hailed as the
most significant and groundbreaking new technology in IVF in decades (see
Van de Wiel,
2017 , 2018 , 2019 ). Its advocates even believe that TLS will eventually
make it possible to recognize chromosomal or genetic deviations in embryos –
an art that currently requires a biopsy analysis during PGD/PGS (field
notes, public lecture at fertility clinic; see also Daughtry and Chavez, 2018 ).
The fuss is apparent in the following snapshot from our field notes from the
2013 Nordic IVF Laboratory Society conference where a TLS advocate is
describing the technology: It’s the first day of the Nordic IVF Laboratory Society conference
and a presentation about the arrival of time-lapse technology is
on. The speaker is an embryologist and is connected to a company
that is marketing an application of the device; she hence
declares herself to be a bit ‘biased’ in that regard. At the
beginning of the presentation, she shows a colourful cartoon
drawing in which embryos drink, smoke and party all night while
the biologists are out of the lab. The cartoon shows how the
badly behaving embryos hear a biologist returning to work and
pretend to be well-behaved while she has a look at them. After
showing the cartoon, the presenter declares pointedly that ‘with
time-lapse, the party is over’: Time-lapse technology enables
staff to check on video to see how the embryos were behaving
while they were not being monitored. This is important because
when left alone, embryos ‘do funny things’. They are ‘naughty’
and ‘deceitful’. The speaker explains that with time-lapse ‘we
can see how they behave’. Only those that have behaved in a
certain way ‘do become babies’ – the naughty ones ‘will not
become babies’.
It’s the first day of the Nordic IVF Laboratory Society conference
and a presentation about the arrival of time-lapse technology is
on. The speaker is an embryologist and is connected to a company
that is marketing an application of the device; she hence
declares herself to be a bit ‘biased’ in that regard. At the
beginning of the presentation, she shows a colourful cartoon
drawing in which embryos drink, smoke and party all night while
the biologists are out of the lab. The cartoon shows how the
badly behaving embryos hear a biologist returning to work and
pretend to be well-behaved while she has a look at them. After
showing the cartoon, the presenter declares pointedly that ‘with
time-lapse, the party is over’: Time-lapse technology enables
staff to check on video to see how the embryos were behaving
while they were not being monitored. This is important because
when left alone, embryos ‘do funny things’. They are ‘naughty’
and ‘deceitful’. The speaker explains that with time-lapse ‘we
can see how they behave’. Only those that have behaved in a
certain way ‘do become babies’ – the naughty ones ‘will not
become babies’.
The advocate implies that the rationale for using TLS is that it produces a
different kind of knowledge about embryogenesis. TLS
offers embryologists more visual and temporal information about embryo
development during the culture process, as the system constantly monitors
the embryo by taking photos every five to twenty minutes. The resulting
videos allow the embryologist to observe and record developmental markers,
such as the timing of cell division and the movements of embryo growth. As
embryologists in our fieldwork clinics told us, they conventionally take ‘a
quick glance’ manually through the microscope once a day to visually examine
the embryo’s static morphological appearance – embryos should not be out of
the incubators for more than two or three minutes, or their pH levels will
drop. TLS knowledge about embryogenesis, reconstructed by its temporality,
may ultimately ‘rewrite the facts of life’, as we discussed with a
conference exhibitor after the presentation described above. Indeed, one
might speak of an epistemic break in the practices of knowing embryos and
their viability (in culture, in vitro ), as the previously
invisible temporal dimension becomes the way of knowing and reproductive
decision-making (see Van de Wiel, 2017 , 2018 , 2019 ).
TLS provide a representation of embryo time which can be manipulated to give
visual access to reproductive processes that were previously too slow to be
observed. Van de Wiel
(2018 : 21) argues that TLS introduce a ‘cinematographic turn’
in IVF clinics, making embryogenesis visible as a process for a varied
audience. TLS-based information, videos and images are shared routinely with
intended parents, allowing patients to visually take part in the scientific
work ( Landecker,
2007 : 123). As Helosvuori (2019) has shown,
when embryos are observed through the microscope in the traditional way,
intended parents are also provided with information about embryo development
and given a role in decisions on embryo selection. In such cases, parents
are only told about embryogenesis and morphology or shown
static pictures of (their) embryos. Nevertheless,
through such information-sharing, patients become enrolled into the process
of knowledge production and even into interventions that render previous
conceptions of embryo viability inaccurate. This happens with ‘pity
transfers’, where embryos that are (perceived to be) inviable are
transferred because the patient wishes it: These transfers sometimes result
in the birth of healthy babies, which in turn leads embryologists to revise
their views on embryo viability ( Helosvuori, 2019 ).
As we hinted at the beginning of this section, patients are aware of TLS and
its additional costs per treatment cycle. It is also one of the few
laboratory technologies directly marketed to patients ( Pottage, 2018 ). Thus, TLS
involves additional clinical and financial decision-making on the patients’
part.
In the following snapshot from a video recording of a clinic appointment, the
embryologist is showing the intended parents an accelerated video of the
cultured embryos collated together on-screen: The embryologist and the intended parent couple are all sitting in
front of a big computer screen. The intended mother gives few
faint shrieks as the video goes on and points excitedly at the
evolving embryo images. The embryologist is simultaneously
explaining about the two embryos chosen for transfer on the same
day: ‘We could take all these fertilized oocytes and look at
them all together. So let’s start [the video] again. Okay. Let’s
follow them [the embryos] here. The first thing that we are
checking was these pronuclei here. So, the division with the
oocyte is okay and the normal pronucleus amount [too]. Very
important. And now the next thing that we are looking at in
these embryos, which is a good sign for an embryo, when it’s
divided on the same day [as] fertilization, and that was on
Saturday, when you were [at the clinic for the egg-harvesting
and sperm sample] in the morning. So the [same] afternoon,
around 25, 26, 27 hours after fertilization, the oocytes start
to, the pronucleus starts to disappear, like this and then it
divides first time [into a two-cell embryo]. So this type of
embryo is, it’s so-called early [cleavage] embryo. And it’s
always when … There has been studies of many embryos in the
literature, so it’s always a good sign for an embryo when it
divides like this. So, I think now this is going as it should
be, divides into two. Here. This is a little bit slower embryo.
… A little bit slower than this one, but dividing very nicely.
[Another one of the embryos chosen for transfer is a] little bit
quicker all the time than this one and now this one follows
here, now it’s here, but still with the right timing and, going
to, you can see this. It’s going nicely. So, there it is at
eight cells and here is eight cells, which is a really, the
right amount of cells in the embryo on day three’. They talk a
bit about the third embryo, which will be cultured until the
blastocyst stage and then possibly vitrified. Then the
embryologist asks if the couple would like prints of the embryo
images. The couple happily accept these and the embryologist
says: ‘I will send it to you. This [too], when we see if the
embryo goes for freezing. So, after that I will send it to you.
But then you had a picture from [a baby], going from, so you can
see the kind of embryos that have been transferred. So you will,
I will send it in the email’. (video recording, clinic C)
The embryologist and the intended parent couple are all sitting in
front of a big computer screen. The intended mother gives few
faint shrieks as the video goes on and points excitedly at the
evolving embryo images. The embryologist is simultaneously
explaining about the two embryos chosen for transfer on the same
day: ‘We could take all these fertilized oocytes and look at
them all together. So let’s start [the video] again. Okay. Let’s
follow them [the embryos] here. The first thing that we are
checking was these pronuclei here. So, the division with the
oocyte is okay and the normal pronucleus amount [too]. Very
important. And now the next thing that we are looking at in
these embryos, which is a good sign for an embryo, when it’s
divided on the same day [as] fertilization, and that was on
Saturday, when you were [at the clinic for the egg-harvesting
and sperm sample] in the morning. So the [same] afternoon,
around 25, 26, 27 hours after fertilization, the oocytes start
to, the pronucleus starts to disappear, like this and then it
divides first time [into a two-cell embryo]. So this type of
embryo is, it’s so-called early [cleavage] embryo. And it’s
always when … There has been studies of many embryos in the
literature, so it’s always a good sign for an embryo when it
divides like this. So, I think now this is going as it should
be, divides into two. Here. This is a little bit slower embryo.
… A little bit slower than this one, but dividing very nicely.
[Another one of the embryos chosen for transfer is a] little bit
quicker all the time than this one and now this one follows
here, now it’s here, but still with the right timing and, going
to, you can see this. It’s going nicely. So, there it is at
eight cells and here is eight cells, which is a really, the
right amount of cells in the embryo on day three’. They talk a
bit about the third embryo, which will be cultured until the
blastocyst stage and then possibly vitrified. Then the
embryologist asks if the couple would like prints of the embryo
images. The couple happily accept these and the embryologist
says: ‘I will send it to you. This [too], when we see if the
embryo goes for freezing. So, after that I will send it to you.
But then you had a picture from [a baby], going from, so you can
see the kind of embryos that have been transferred. So you will,
I will send it in the email’. (video recording, clinic C)
Note that TLS seems to fulfill both an affective and a clinical diagnostic
function here. The embryologist straightforwardly juxtaposes pictures of
viable embryos with baby pictures, not unlike ultrasound images and videos.
As with ultrasound, prenatal life in TLS imaging videos is known without the
embodied, experience-based knowledge of the intended mother (see e.g. Duden, 1993 ;
Homanen,
2013 ). However, unlike ultrasound, TLS places the prenatal life
concretely outside the maternal body and rewrites the human origin story
accordingly ( Van de
Wiel, 2017 , 2018 ). Nevertheless,
encountering prenatal life – seeing ‘the baby’ for the first time and
getting a first picture – is the obvious attraction for the intended
parents.
The embryologist in the snapshot also seems to be promoting the notion that
there is a universal regularity in the temporal process of embryo
development that can be both observed and operationalized to
predict viability (see Waldby, 2019 ). Here, she refers
to studies of embryo development, but TLS also have a data-driven component.
This component allows visual information about temporal and morphological
features (which are sometimes invisible to the human eye) to be measured,
quantified and analyzed through algorithms to predict embryo viability.
The algorithms are based on historical data sets: The timing of cellular
divisions is viewed in light of historical embryo populations to predict
success rates, that is, the likelihood that the treatment will result in
pregnancy. Clinics are also encouraged to provide their own data for the
further development of the algorithmic tools. In principle, then, TLS allow
clinics to adopt a quantified, automated, standardized, data-driven method
for knowing about viability and selecting embryos through prediction (see
Van de Wiel,
2018 , 2019 ).
Where TLS run automated algorithms to predict the viability of embryos cultured
at a clinic, one should ideally be able to use this to scale up production
by standardizing one’s knowledge production. Data-based prediction is
marketed as making it possible to transfer embryos at an earlier stage than
would normally be the case, allowing clinics to accommodate more patients
with a better success rate.
During our fieldwork, not all clinics took full or even any advantage of this
data-driven component, and many embryologists relied at least partially on
manual appraisals of embryos, either under the microscope or by rewinding
TLS videos backwards and forwards on the computer screen. Embryologists
described how one develops ‘an eye’ and ‘a feel’ for embryos after observing
them for a long time. This experience-based, hands-on method of examining
embryos (i.e. craft know-how) was called ‘a natural way to rule out embryos’
by one of our informants. Some, however, downplayed their experience-based
observational skills in embryo examination, regarding it as pointless in
comparison with standard quantified information on embryos. This shows that
embryologists work at the crossroads of standardized and tacit modes of
knowledge production, and that technologies can be used in non-standard and
non-automated ways.
Despite TLS’s acclaimed potential to produce valuable information about
embryos, its translation into clinical use is not clear-cut. To take full
advantage of the technology, staff training and a lot of extra time in the
laboratory would be required. ‘One could spend half a day tinkering with
them [TLS]’, laughed one embryologist in our study. On the other hand, the
meaning of all the markers of embryo development on which TLS reports is not
fully known. For instance, we were told that in light of historical data
sets, it is believed that cells should divide in a ‘disjunct manner’ so that
the cell ‘is not doing something all the time’. However, when we asked
further about the meaning of this, we were told that there is no knowledge
about what it specifically means for cell quality, let alone for further
embryo development.
Predictive
Knowing developmental time in the IVF process (through predictive TLS in
incubators or by manual e/valuation) affects the decisions on the duration
of embryo culture in incubators: For how many days after fertilization
should the lab culture embryos that are candidates for transferral to an
intended mother’s uterus? There seems to be no strong consensus among
clinicians about which transfer stage results in more pregnancies or about
the health implications of this for IVF-born children. Clinics mostly follow
their own experience-based assessments and small-scale statistics and
practice accordingly. Thus, the duration of embryo culture varies, leading
to different stages of embryogenesis at transfer.
The embryologist places the eggs and sperm on a petri dish on the day of
ovarian pick-up (OPU), that is, the day when eggs are harvested from the
ovaries. Two preliminary nuclei (one from the egg and one from the sperm)
signify fertilization one day after OPU (day one). Markers indicate whether
the cells have begun cleavage (i.e. to form an embryo) two days after OPU
(day two). There are six to twelve cells on day three; the morula stage is
reached on day four. A blastocyst forms ‘roughly on time’ by days five to
six.
The main stages at which embryo transfer is performed are the cleavage stage
(days two to three after fertilization) and the blastocyst stage (days five,
six or even seven after fertilization). Some of our field clinics advocated
the ‘long culture’ process of five to six days and some preferred the ‘short
culture’ of two to three days. Some even changed their preferences and
practices during our fieldwork period. According to our informants, public
university hospitals routinely used the short culture to accommodate more
patients and save resources.
In our fieldwork clinics, the short culture was argued for in terms of economy
and the superiority of the ‘natural’ womb environment. The economic
arguments referred not to the cost-effectiveness of treating as many
patients as possible, as fast as possible, with the fewest resources (even
though this might also have been taking place), but rather to being
economical in the face of the chronic uncertainty of prediction that
characterizes the IVF treatment sector. One never knows if embryos that look
viable on days one to three will survive until the blastocyst phase.
Especially with poor-quality embryos, medical staff were keen on cleavage
stage transfer ‘so that there is at least something to transfer’, as one
embryologist put it. These arguments were based on the belief that the womb
environment is always better for embryo development than the artificial
incubator and growth medium, placing hope in the natural(ized) in
vivo environment to enable viability. This belief was further
underpinned by the uncertainty regarding whether embryos that are judged to
be of good quality (according to morphology and developmental biomarkers)
really implant more often than bad-quality embryos (see Thompson, 2005 :
114). Some professionals at laboratories with TLS also relied on the
system’s predictive analysis and standardized use: What need is there for
the long culture if one can predict longer-term viability?
The prediction of viability is also questioned by professionals. Sometimes
markers that appear to be unpromising turn out to be meaningless in a long
culture, again because of uncertainty regarding the meaning and relevance of
all the stages in development and morphological characteristics. This is
apparent in the following interview extract: Q: Could you explain once more what you observe from the
embryos? A: So we observe in day two and three the cell quantity, … how much
fragmentation there is [a sort of graininess on the embryo] and
then we have a look at the cells, whether they are the same or
different size, it’s better if they are similar size. … Then we
have a look at the nuclei, is there a nucleus in every cell. If
there are multiple nuclei, that is a bad situation, then there
has been something wrong in the cleavage. Q: But that can be fixed later on, is that right? A: Yes, that can be fixed. We used to be much more critical toward
multiple nuclei and so we dumped those always, mostly, when we
saw even one cell with multiple nuclei. But now we have noticed
that when they are transferred, it can get fixed, so it is not
such a critical factor after all. (embryologist 1, clinic A)
Q: Could you explain once more what you observe from the
embryos?
A: So we observe in day two and three the cell quantity, … how much
fragmentation there is [a sort of graininess on the embryo] and
then we have a look at the cells, whether they are the same or
different size, it’s better if they are similar size. … Then we
have a look at the nuclei, is there a nucleus in every cell. If
there are multiple nuclei, that is a bad situation, then there
has been something wrong in the cleavage.
Q: But that can be fixed later on, is that right?
A: Yes, that can be fixed. We used to be much more critical toward
multiple nuclei and so we dumped those always, mostly, when we
saw even one cell with multiple nuclei. But now we have noticed
that when they are transferred, it can get fixed, so it is not
such a critical factor after all. (embryologist 1, clinic A)
Embryos may develop and implant normally further along the line. There are also
genome abnormalities that cannot be predicted in early-term cultures.
Recurrent early miscarriage, for example, may be a sign of problems with the
sperm genome: It is believed that the genome in the sperm is only activated
in the embryo after day three. Problems will therefore not manifest
themselves during the cleavage stage and cannot be predicted without
PGS/PGD.
Both of the above cases are also good examples of problems not just with
prediction in general, but with TLS prediction in particular. TLS analyses
are not (yet) sensitive to most chromosomal abnormalities, nor do they take
new or local conditions into account very well. This is because they are
based on historical data sets and not all clinics enter
their own embryo population data into the data pool ( Van de Wiel, 2018 ).
Moreover, in contrast to the hype around TLS, some clinics have almost stopped
using it. Long culture advocates at some of our fieldwork clinics told us
that they did not need the (far-from-foolproof) predictive component of TLS
because it did not really benefit clinical IVF outcomes unless one was set
on doing only short cultures. Here, TLS was described as ‘merely a good
incubator’ and thus as too expensive for clients.
The head doctor explained to me in his office: ‘It is of course
interesting to see the temporal development [on-screen] and find
out exactly how the cell can fix itself, but it does not matter
[that much] clinically what the journey has been like until
blastocyst if it looks pretty. … When you master the long
culture [manually] in the laboratory, you don’t need TLS
anymore. It is only useful when you don’t have the skill to keep
the embryos alive [until blastocyst]. … This idea of the womb
always being like a warm embrace for the embryo is just not true
because the womb is better on day five or six’ [than days two to
three, referring to the endometrium being more receptive at that
stage of the IVF cycle]. He then went on to elaborate on how
there are ways to test the stage of the endometrium to define
the exact individual implementation window for the transfer and
how that combined with PGS/PGD is the way to IVF success. (head
doctor, clinic F)
The head doctor explained to me in his office: ‘It is of course
interesting to see the temporal development [on-screen] and find
out exactly how the cell can fix itself, but it does not matter
[that much] clinically what the journey has been like until
blastocyst if it looks pretty. … When you master the long
culture [manually] in the laboratory, you don’t need TLS
anymore. It is only useful when you don’t have the skill to keep
the embryos alive [until blastocyst]. … This idea of the womb
always being like a warm embrace for the embryo is just not true
because the womb is better on day five or six’ [than days two to
three, referring to the endometrium being more receptive at that
stage of the IVF cycle]. He then went on to elaborate on how
there are ways to test the stage of the endometrium to define
the exact individual implementation window for the transfer and
how that combined with PGS/PGD is the way to IVF success. (head
doctor, clinic F)
This head doctor sketches a wholly different picture of TLS as a clinical tool
compared with industry advocates or with what the technology’s worldwide
sales figures might suggest (e.g. Van de Wiel, 2019 ). Instead of
celebrating detailed knowledge of embryogenesis for clinical purposes, he is
of the opinion that TLS is rendered redundant by skilled laboratory work
learned through repeated performance over time. He does not share the
conception that embryo transfer in the blastocyst phase can be justified
with arguments about the caring in vivo uterine environment
because the optimal time for implantation is understood to be around days
five to six, with some individual variation.
Long culture is also perceived as economic, but in somewhat opposite ways to
short culture. When long culture is mastered, it is believed, viable embryos
are likely to survive. This saves money and labor for all: It really is a lot more cost-effective, in a way, if we continue
[to culture] to day five because many times it can occur that in
day two, there are a lot of embryos, and then you transfer one
of them into the uterus, and many into the freezer, and then you
transfer those day two embryos [later]. It can happen that the
patient undergoes multiple transfers with frozen embryos and not
with great odds. However, if you continue to day five, you sort
of weed out useless [non-viable] embryos … and then the odds per
transfer are much higher. (doctor 2, clinic A)
It really is a lot more cost-effective, in a way, if we continue
[to culture] to day five because many times it can occur that in
day two, there are a lot of embryos, and then you transfer one
of them into the uterus, and many into the freezer, and then you
transfer those day two embryos [later]. It can happen that the
patient undergoes multiple transfers with frozen embryos and not
with great odds. However, if you continue to day five, you sort
of weed out useless [non-viable] embryos … and then the odds per
transfer are much higher. (doctor 2, clinic A)
‘Cost-effectiveness’ refers to both patients’ and clinics’ interests. The
professionals explained to us that transferring as many embryos as possible
with the least effort is not good for business at the end of the day. The
pregnancy results remain low and freezing multiple embryos also takes time
and effort. Patients are burdened with repeated disappointments and
unnecessary medical interventions. It is more lucrative to culture for
longer and to transfer and freeze less. According to this industry logic,
good news will eventually travel, meaning that in addition to better
clinical IVF outcomes, business outcomes improve too.
The business logic, then, does not exclude care for patients or cells, but
requires it. Patients’ wishes and practical everyday lives affect the
culture duration in other ways as well. Craft is about practicalities (e.g.
Meskus,
2018 ). Cleavage stage transfers may be made for patients who
want their transfer to be conducted by a particular doctor who can only
perform the transfer on the second day of embryo culture. National holidays
are often accommodated. Furthermore, if a patient is eager to ‘get to the
point of embryo transfer’ – to ‘push the panic button’, as put in the words
of one informant (doctor 2, clinic A) – rather than waiting a couple of days
and incurring the risk that the embryos might perish by days five to six, a
transfer is made to please them.
Overall, TLS are designed to enable an automated, standard way of knowing
embryo viability in terms of embryogenesis and morphology and are thus
designed to enable the scaling-up of production. As with standards and
standard technologies more generally, they are subject to local adjustment
and manipulation in practice ( Timmermans and Epstein, 2010 ).
The unpredictability, uncertainty, locality and individuality of embryo
viability make it hard for the TLS standard to work and for clinics to
capitalize on it. Furthermore, there are practices that resist this
automation and standardization for its own sake, for the sake of the
intended parents’ lives and finances as well as for those of the clinics.
Here, craft has both economic and ethical value.
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