Laboratory Guide for Patients

Welcome to Cambridge IVF!

We realise that the laboratory is often a place of great mystery and intrigue to you as you don’t get the opportunity to spend any time within that environment as part of your treatment pathway. That is for very good reason, we run the laboratory as a clean room so entry is restricted to just the embryologists who wear special clothing, hats and gloves to ensure no contamination is brought into the laboratory.

This document has been designed to give you some insight into what happens between the collection of your sperm and eggs and your embryo transfer. It’s a chance for you to see your treatment cycle through the eyes of your embryologist!

We realise that this booklet cannot answer every question everyone will think of so if you still have any questions ask away as we are, after all, here for you!

So without further ado let’s turn the page and begin our journey together starting with your egg collection…

Day 0 – Your Egg Collection

On the morning of your egg collection you will arrive at Cambridge IVF and be admitted to our ward area ready for your trip to theatre. Whilst you are having your eggs collected we will prepare the sperm sample from your partner or donor which will be used to inseminate your eggs later in the day. We use a microscope to identify the eggs which are surrounded by a cloud of cells called cumulus from the fluid the doctor collects from your follicles. We then wash the eggs and place them in the incubator in a culture medium which is designed to give them the nutrients they need until we are ready to inseminate the eggs the same afternoon.

After your egg collection a member of our laboratory team will speak to you and confirm with you the number of eggs we collected, the quality of the semen sample and the insemination method we intend to use (IVF, ICSI or MACS-ICSI) to fertilise your eggs.

Following on from the semen analysis you would have had prior to treatment or the information we hold on your selected sperm donor we already have a good idea what the best treatment option will be but sometimes things can change on the day so we are always flexible in our approach to ensure that you get the very best chance of a successful outcome from your treatment cycle.

Oocyte Vitrification (Egg Freezing)

If you are freezing eggs this is performed on the day the eggs were collected, usually around 2 hours later. We gently remove the cells that naturally surround the eggs to allow to see if the eggs are mature. We then freeze the mature eggs using a process called vitrification. It’s the same technique we use for embryo freezing on day 5 or day 6. Survival rates when thawing are good, we expect around 90% of your eggs to survive. We store your eggs in pairs on specific devices meaning we do not have to get all of your eggs out at the same time. Because we have to remove the cells from around the egg before we freeze them your eggs can then only be fertilised using the ICSI technique described below when you come back to use them.

In-Vitro Fertilisation (IVF)

The prepared sperm sample is mixed with the eggs in a petri dish. We do not use test tubes to inseminate eggs any more, things have moved on a lot since then! This process is witnessed using our electronic witnessing system which adds another layer of security in our commitment to preventing laboratory errors occurring. The only sperm that will match your eggs is the one we prepared for you. The procedure is fast and within 3 minutes your eggs are back in the incubator and the fertilisation process is underway!

Intracytoplasmic Sperm Injection (ICSI)

ICSI takes the insemination process a little further and involves the injection of a single sperm into each mature egg using a very fine pipette. We carry out this procedure when we believe that there is a significant chance that the sperm and eggs may not fertilise well using the IVF technique. Following the injection procedure the eggs are returned to the incubator overnight. If you are using the Embryoscope system your eggs will be transferred to the Embryoscope following the ICSI procedure.

We can only perform ICSI on mature eggs (we can easily spot an egg which is mature using the microscope). It is normal for some eggs to be immature so be prepared for this when we call the day following egg collection to let you know how the fertilisation procedure has gone.

Magnetic Activated Cell Sorting (MACS)

MACS-ICSI involves the use of magnetic beads which attach only to poor quality sperm. The sperm are then passed through a magnetic filter and the poor quality sperm are trapped leaving only the good ones to pass through. These are then used for treatment in exactly the same way as the standard ICSI process.

MACS-ICSI will benefit couples where the man is known to have elevated levels of DNA fragmentation in his sperm and for people who have experienced miscarriage or failure to develop good quality embryos with standard ICSI. If we feel you are going to benefit from MACS-ICSI treatment we will have already discussed this with you.

The published scientific evidence suggests that MACS-ICSI will benefit treatment by increasing the number of embryos suitable for transfer or freezing and also reducing the risk of miscarriage.

On average we would expect approximately 60-70% of injected eggs to fertilise normally from ICSI or MACS-ICSI. This is approximately the same number of eggs we expect to fertilise from IVF. The average may be lower for patients using sperm which has been recovered surgically or for patients where we know the egg quality is variable.

The EmbryoscopeTM

The Embryoscope combines a microscope with an incubator allowing us for the first time to offer truly uninterrupted embryo culture. The system takes an image of each developing embryo every 10 minutes and collates these together into a time-lapse video for each embryo. We get to see everything the embryos are doing and can use an additional range of tools based not just on how they appear but also on their development through time to select the best embryos for transfer or freezing.

The scientific literature suggests an improvement in pregnancy rates from the use of the Embryoscope system.

In our experience the benefit appears to be around 10% and is more significant in women over the age of 38.

If you are using the Embryoscope we will transfer the eggs in immediately after the ICSI or MACS-ICSI procedure. For IVF cases we need to perform the fertilisation check procedure on day 1 before we transfer the eggs to the Embryoscope to ensure the cumulus cells that naturally surround the eggs have been removed so the Embryoscope camera can clearly see the eggs in culture. Embryoscope allows us truly uninterrupted culture meaning that we do not need to remove the dish containing the eggs / embryos until your embryo transfer. This prevents stress to your developing embryos due to changes in temperature, pH and light intensity when we move them. The human uterus does not have a door for a very good reason; embryos thrive when they are left alone!

Embryoscope technology also allows us to calculate a known implantation data (KID) score on days 3 and 5 of your cycle. KID scores help us to identify which is your best embryo for transfer in a way which is not dependent on a single appraisal of how the embryo looks but is reflective of how it has grown through time. KID is based on data from thousands of embryos which resulted in a live birth and is a very helpful tool to assist us to ensure you get your best embryo back first, reducing the time and costs involved in your journey to parenthood as much as possible.

Day 1 – Fertilisation Check

Ok, it’s now day 1, we all hope that things have gone well overnight but now we need to find out how many of the eggs have fertilised. No matter how we fertilised the eggs yesterday with IVF, ICSI or MACS-ICSI, the procedure for fertilisation check is an important step in your treatment cycle.

We are looking for signs of ‘normal’ fertilisation and it’s easy to spot this using the microscopes we have in the laboratory for IVF cases, or the Embryoscope video information that we have collected overnight for ICSI and MACS ICSI cases.

A normally fertilised egg should have 2 ‘pronuclei’ (the male and female genetic information which you can see as 2 small circles within the egg) which are evident at the time of fertilisation check (around 18 hours after the insemination or injection of sperm). If an egg is seen to have more than 2 pronuclei then this has fertilised abnormally and is separated from the normally fertilised eggs. This kind of egg is unsuitable for use in your treatment as it could lead to an abnormal pregnancy. Where an egg shows just one pronucleus this can still be genetically normal so we continue to culture these and ensure we keep them separate throughout the culture process.

We will call you on the morning of the Fertilisation Check, usually before 10:30am, to let you know how things have gone so it’s important that you keep close to the telephone number you gave us as we know you will want to know as soon as possible. If you had IVF treatment using Embryoscope, your eggs will be loaded into the Embryoscope after fertilisation check.

Day 2 – Early Embryo Development

The fertilised eggs should by now have formed 2-5 cell embryos. If you are not using Embryoscope culture, we do not check the embryos on day 2 as we try to minimise unnecessary disturbance to your embryos; they are much better left alone to develop as well as they can. If you are having Embryoscope treatment we do have a look at the videos that have been generated as we can do that without disturbing the embryos, that’s the advantage of Embryoscope! We use the UK national grading scheme to give each embryo a grade which allows us to give you an indication of their quality. Each embryo is an individual and we don’t expect all of them to be top grade, it’s perfectly normal to have a mixture of grades of embryos, some looking stronger than others but at this stage we cannot accurately predict which of your embryos is likely to be the best as they are still very young.

Pregnancies are still obtained from the transfer of embryos we have not graded highly so don’t be disheartened if we have not graded your embryos as top quality. The main thing is they are healthy and continuing to develop and we will continue to check in on them over the next few days to ensure they are growing as expected. We will always be honest with you; if your embryo quality is low we will ensure you are made aware of this and what it means for the outcome of your treatment cycle.

Day 3 – Embryo Grading

Your fertilised eggs should continue to develop on and by now have formed 6-10 cell embryos. We will check this on the morning of day 3 for all cases, including those not using Embryoscope. We use the Embryoscope at this point to determine your Day 3 KID Score which helps us to determine how well your embryos are growing. Again, remember each embryo is an individual and we don’t expect all of them to be top grade, its normal to have a mixture of grades and the differences between your embryos will now start to become more apparent.

Embryo culture conditions have improved dramatically over the last decade and particularly with the use of Embryoscope and the information that it provides. We believe that there is a significantly reduced benefit to a day 3 embryo transfer, even in cases where embryo quality is poor. Day 5 transfers are more synchronous with natural conception and it is important to know that the embryo has proven its capability to develop beyond day 3 and thus its ability to create a pregnancy. Therefore, our routine recommendation is to perform all embryo transfer procedures on day 5. Your embryos will remain in culture until that day, undisturbed in an optimal environment for their onward development. In certain rare cases we may still advise embryo transfer on day 3 and if we feel this would be in your best interests we will discuss this with you.

Day 4 – The Day of Rest (but a lot going on)

During day 4 the embryos undergo a transition we call compaction and early blastulation. If you are having Embryoscope treatment we will review the video information again on day 4 as we can do this without disturbing your embryos, otherwise we will leave them well alone!

Day 5 – Blastocysts Begin to Form

By day 5 following egg collection some of your embryos (typically around 50%) should have started developing into blastocysts. Blastocysts look very different to early embryos, the cells are now starting to specialise into those which will form the baby and those that will form the placenta. This is also the first stage where the embryo begins to increase in physical size!

The blastocyst will hatch from the protective ‘shell’ which has surrounded the embryo through its development, the Zona Pellucida, and once free from this shell, the blastocyst can implant into the lining of the womb and hopefully form a pregnancy.

As the blastocyst is a more advanced development stage we know that embryos which form good quality blastocysts have good implantation potential. Your blastocysts will be graded on the morning of day 5 using a nationally approved blastocyst grading scheme and we will select the one (or possibly two) strongest looking blastocysts for transfer. We can also use the Embryoscope at this point to determine your Day 5 KID Score which helps us to select your strongest blastocyst for transfer. In cases where no blastocysts have formed but embryos are still growing we will transfer the most advanced embryos as blastocyst formation takes place over day 5 and day 6.

We will call you between the hours of 8:00 and 10:00 on day 5 to confirm the plan for embryo transfer if you have decided to proceed with fresh embryo transfer. If you have opted for the ‘Elective Embryo Freezing Program’ program we will advise how many blastocysts are suitable for freezing using the vitrification technique.

Your Embryo Transfer

Your embryo transfer (ET) will usually take place on day 5 of your treatment cycle at the time agreed with you. The ET is usually a very straightforward and painless experience and will take around 30 minutes.

You should bring your partner or a friend with you if possible as we would prefer you to have a chaperone and someone to take you home after the procedure.

We will ask you to arrive for your ET with a full bladder so drink a bottle of water of juice 60 minutes before your appointment time. This helps us during the transfer procedure as the fluid in the bladder makes the ultrasound view very clear.

We will confirm with you the number of embryos for transfer and let you know the quality, and then ask you to sign the consent prior to the embryo transfer taking place.

You don’t need to rest after an ET, lying on your back for hours or even days afterwards will not help the embryo(s) implant and in truth may do more harm than good. We recommend you take things easy so just try to carry on with your life as normal but act as if you are pregnant.

What if there are no suitable Embryos for Transfer?

Unfortunately it is not always the case that there are embryos for transfer. This can be because no normal embryos developed or because the embryos that did develop have not thrived and have stopped developing. This usually happens between day 3 and 5. In such cases we may advise you not to proceed with transfer as the chance of pregnancy is dramatically reduced. We realise that this will be a very distressing situation for you and if you feel that you would prefer to have an embryo transfer for your own wellbeing we will of course respect your wishes and proceed with a transfer.

Rest assured that in the event that there are no embryos to transfer on day 5, if we had performed an embryo transfer earlier in the cycle, on day 3 for example then the ultimate outcome would have unfortunately been the same. The advantage of proceeding to Day 5 before deciding, is we get as much information as possible from the EmbryoScope data prior to transfer, which we can use to guide you if you decide to proceed with another future treatment cycle.

Elective Single Embryo Transfer (eSET)

The Human Fertility and Embryology Authority (HFEA) advised all UK Fertility Centres in the UK to develop a strategy to minimise multiple births with effect from 1st January 2009.

Although the prospect of a twin pregnancy may sound attractive you need to be aware of the risks not just to the developing children but also to yourself and the long term effects that it could have on you and your family.

Cambridge IVF is committed to facilitating safe and effective fertility treatment and we take our commitment to reduce unnecessary multiple births very seriously. With this in mind we have constructed an algorithm to determine which patients would benefit from eSET based on their age, treatment history and embryo or blastocyst quality and we will inform you what we believe to be the best strategy for you at the time of your embryo transfer.

For more information pertaining to the risks of multiple births please visit the HFEA website (opens in a new tab).

Day 6 – Blastocysts are Still Growing, are there any more we can Freeze?

The window of time for blastocysts to form is day 5 and day 6. Just like a race, not all of the embryos will finish at the same time. We re-assess your remaining embryos on day 6 and if any more have formed blastocysts of suitable quality we will freeze them for you today. There is no additional fee if we freeze blastocysts on both days; this is covered in the single fee you have paid to freeze your blastocysts.

Once we have frozen blastocysts on day 6 this ends your treatment cycle. Any remaining embryos not suitable for freezing and any eggs remaining in culture will be either discarded or allocated to research or training according to your wishes in the consent forms you completed at the start of your treatment cycle.

Blastocyst Vitrification – Freezing your Embryos for Future Use

Good quality surplus blastocysts can be frozen individually on day 5 or day 6 following your embryo transfer. We use a process called vitrification to rapidly freeze your blastocysts which we then store in our Cryostore for you to use at any time in the future within the time period you have consented to.

After your embryo transfer, on day 5 and day 6 we will look at all the remaining embryos and decide if any of them are strong enough to be frozen and we will let you know how many are suitable. Of course it’s your choice, you don’t have to have them frozen if you don’t want to, we will carry out your wishes either way but you should spend some time before your embryo transfer deciding what you would like to do if you do have embryos available to be vitrified. Approximately 90% of blastocysts will survive the process and results from frozen embryos are comparable (or in some age groups even higher) to those from fresh embryo transfer so freezing blastocysts is a very cost effective way to extend your treatment options.

Elective Embryo Freezing Program

There are two reasons why we may recommend freezing all blastocysts of suitable quality rather than proceeding with a fresh embryo transfer.

1. Freeze all embryos for medical reasons.

In some cases it may be necessary for us to recommend that you freeze all of your suitable quality embryos because you are at risk of ovarian hyper stimulation syndrome (OHSS). If this is the case the doctor will advise you on the day of egg collection that this is our medical recommendation. By not performing an embryo transfer we greatly reduce the risk of you experiencing severe OHSS which may result in hospitalisation and can ultimately be life threatening in very rare cases. There are other medical reasons for recommending freezing rather than transferring embryos, such as the presence of fluid in the uterine cavity, thin endometrium or polyps /fibroids. In the event that these apply to you the doctor will discuss this with you and advise freezing embryos.

2. Elective embryo freezing.

In some age groups, typically women over 38 years of age, we see a significant difference in the pregnancy rates from fresh and frozen embryo transfer, in that rates from frozen embryo transfer are higher. We believe this may be due to reduced uterine receptivity in the medically manipulated menstrual cycle in which your eggs were collected in this patient age group. By choosing to electively introduce a ‘treatment pause’ after your embryos have grown to blastocysts and been frozen you can allow your body to recover from the procedure and return to have a frozen blastocyst thawed and replaced in a more natural menstrual cycle. By doing so you can take advantage of a higher chance that that treatment will result in a pregnancy.

Clinical Results

For more information regarding the success rates our patients achieve from treatment at Cambridge IVF please visit our website (opens in a new tab).

Comment on Witnessing

We are all very aware there have been IVF mix-ups in other clinics in the UK and across the world. Cambridge IVF has taken every step possible to minimise the risk of mix up occurring here and we are very proud that since we opened in 2011 we have never had a mix up event occur.

In addition to stringent checking and procedural controls being in place, we have invested in an electronic system called RI Witness which provides a further layer of transparent and auditable protection against the mixing of incorrect sperm and eggs or transfer of the incorrect embryos in your cycle. We are not saying we are likely to have made a mistake without it, this could not be further from the truth but we do believe in making our processes as safe and risk free as possible and we believe that RI Witness ensures this. We also believe it is right to inform you that such risks exist and we do everything possible to reduce them.

We hope you have found this booklet informative and interesting. We realise we may not have covered all of your questions so if you do have any other queries we are here to help so please contact us via any of the means below;

How to get in Touch

Cambridge IVF
Kefford House
Maris Lane
Trumpington
Cambridge
CB2 9LG

• Switchboard: 01223 349010
• Email Cambridge IVF
• Our Cambridge IVF website (opens in a new tab)
• Follow us on Twitter (opens in a new tab)