Laboratory methods

There is a wide range of laboratory methods that can be used in your fertility treatment, these are very often called add-ons by the Human Fertilisation & Embryology Authority (HFEA). The add-ons are certain techniques that may have shown some promising results in studies or have been around for a number of years, but have not necessarily been proven to improve pregnancy or birth rates. 

The HFEA have come up with a system of traffic lights to list these add-ons and indicated whether certain techniques are supported by any evidence or research on improving pregnancy or live birth rates. For more details follow this link

We have listed below the most common ones with further details.

ICSI 

ICSI (Intra-Cytoplasmic Sperm Injection) is a micromanipulation technique where an individual sperm is injected into an individual egg. Before ICSI, men with a very low sperm count had a poor chance of fathering a child even with other reproductive technologies. With ICSI, only one motile sperm for each egg retrieved is needed. This enables men with very poor sperm counts to achieve fertilisation, produce embryos suitable for transfer, pregnancy and the birth of healthy children. ICSI can be performed using sperm retrieved by testicular sperm extraction in men with azoospermia (lack of sperm ejaculate).

ICSI can be carried out on eggs retrieved through stimulated or natural cycles and is often recommended in those who have experienced failed fertilisation using standard IVF.

Cost of ICSI is chargeable on top of your treatment fee.

  • ICSI costs

    • ICSI – Intracytoplasmic Sperm Injection
      £950.00


PICSI

Physiological Intracytoplasmic Sperm Injection (PICSI) is a method of sperm selection which is in addition to ICSI. It copies the process where mature sperm bind to the zona pellucida shell surrounding the egg.

PICSI helps embryologists in sperm selection. It is based on research documenting that mature and structurally sound sperm will bind to hyaluronan, and is a reliable alternative to more expensive DNA integrity assays.

Indication for PICSI include:

  • Low sperm count or morphology
  • Previously low number of fertilised eggs or failed fertilisation after ICSI
  • High sperm DNA fragmentation results
  • Repeated miscarriage and/or repeated embryo transfer without implantation

Scientific studies do not show that this technique adds risks to the ICSI procedure and PICSI may not increase your chance of having a baby, but using this technique will help the embryology team when selecting the sperm for injection.

As the use of PICSI is not evidence based with respect to improving livebirth rates and is optional, the clinic will only offer it when your consultant deems it appropriate for your treatment. City Fertility will offer PICSI in order to reduce the chance of having a miscarriage. 

Treatment add-on

PICSI is outlined as additional treatment options by the Human Fertilisation and Embryology Authority (HFEA) and have currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that they are effective at improving the chances of having a baby for most fertility patients. For more information on this add-on, please follow the link provided.

Risks

As per HFEA “PICSI is a non-invasive test performed on a semen sample as an additional step in the ICSI process. The risks associated with the use of ICSI also apply to PICSI. However, PICSI does not carry any additional known risks for the person undergoing fertility treatment or the child born as a result of fertility treatment.

If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.”

Clinical Evidence

As per HFEA “There have been several studies comparing PICSI with standard ICSI, but there is very little evidence to suggest any benefit of using it. A large RCT was recently carried out which showed that using PICSI did not increase the chances of having a baby.

The results of this large RCT did suggest that PICSI may be beneficial in relation to a potential reduction in miscarriage. It is important to keep in mind that this evidence was the secondary outcome, that is, it was not the aim of this research. This means that the study was not designed to investigate the effect of PICSI on miscarriage rate, making these secondary results less reliable. For this reason, it is important to discuss your individual circumstances with your doctor.

At the October 2019 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for PICSI. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage.

This Cochrane review has further information on the evidence for PICSI.”

Costs

Cost of PICSI is chargeable on top of ICSI charge in addition to your treatment fee.

  • PICSI costs

    • ICSI – Intracytoplasmic Sperm Injection
      £950.00
    • PICSI in addition to ICSI
      £240.00

      PICSI is outlined as additional treatment options by the Human Fertilisation and Embryology Authority (HFEA) and have currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that they are effective at improving the chances of having a baby for most fertility patients. For further information please follow this link.

      Cost of PICSI is chargeable on top of ICSI charge in addition to your treatment fee.


IMSI 

Intracytoplasmic Morphologic Sperm Injection (IMSI) is a method of sperm selection which is used in addition to ICSI. At City Fertility the sperm are obserrved on the ICSI microscope while magnified 800 times to allow the embryologists to see the detailed structure of each sperm. Sperm with a good shape (morphology) and little to no vacuolation wiwthin their head region are then selected for the ICSI procedure.

Potential IMSI indications include:

  • Low sperm count AND morphology
  • Previously low number of fertilised eggs or failed fertilisation after ICSI
  • Repeated miscarriage and/or repeated embryo transfer without implantation
  • Poor embryo quality following IVF or ICSI

Scientific studies do not show that this technique adds risks to the IMSI procedure and IMSI may not increase your chance of having a baby, but using this technique will help the embryology team when selecting the sperm for injection. Some studies have shown higher fertilisation rates and an increase in chance of pregnancy where poor ICSI fertilisation has been seen in previous treatment cycles, and when men are apparently fertile however the female partner is older (at least 37 years). 

Treatment add-on

IMSI is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients.For more information on this add-on, please follow the link provided.

Risks

As per HFEA “IMSI is a non-invasive test performed on a semen sample as an additional step in the ICSI process. The risks associated with the use of ICSI also apply to IMSI. However, IMSI does not carry any additional known risks for the person undergoing fertility treatment or the child born as a result of fertility treatment.

If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.”

Clinical Evidence

As per HFEA “There have been several RCTs within the last decade. Systematic reviews suggest that IMSI could be beneficial in specific situations such as previously failed ICSI attempts. The research that has been carried out does not support the use of IMSI over standard ICSI. One small study found that IMSI had improved pregnancy outcomes in older patients, however this study was carried out with a small number of participants and the link, if any, between IMSI and older eggs is not fully understood.

At the October 2020 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for IMSI. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage.

This Cochrane review has further information on the evidence for IMSI.”

For further information regarding this treatment add-on, please visit the HFEA website using this link.

Costs

Cost of IMSI is chargeable on top of ICSI charge in addition to your treatment fee.

  • IMSI costs

    • ICSI – Intracytoplasmic Sperm Injection
      £950.00
    • IMSI in addition to ICSI
      £240.00

      IMSI is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients. For further information please follow this link.

      Cost of IMSI is chargeable on top of ICSI charge in addition to your treatment fee. 


Extended Cultivation

A blastocyst is the embryo stage typically seen five days after fertilisation. A blastocyst has two areas that the embryologists assess, the outer surface of the blastocyst called the trophectoderm which becomes the placenta and an inner group of cells called the inner cell mass which develops into a baby.

If embryos look similar at earlier stages, keeping the embryos until they reach this stage allows the embryologist to choose the best quality embryo(s) for transfer and can improve the chances of pregnancy. Not all embryos will reach the blastocyst stage and it may only be recommended when enough eggs have been fertilised. In addition to using extended culture as a selection tool, we know that in a natural pregnancy, a 3 day old embryo resides in the tubes and reaches the uterus on day 5 or 6. By transferring the embryo to the uterus on day five, the embryo is being returned to a more natural environment mimicking natural pregnancy. Blastocysts are suitable for genetic testing and can be successfully cryopreserved.

Extended Cultivation is included free of charge in all of our treatment packages (where applicable).


Time-lapse imaging of embryos

Using a time-lapse incubator is the latest technology for continuous assessment and culture of embryos. Until recently, embryo monitoring has involved the removal of embryos from an incubator for microscopic assessment at a specific moment in time. GENNET City Fertility offers time-lapse imaging of embryos utilising the EmbryoScope™ – with a microscope and camera system integrated within the incubator your embryos are monitored 24 hours a day whilst they are in culture allowing embryo development to be assessed and observed as a time-lapse movie.

In addition, there is reduced disturbance to your embryos compared to using traditional incubation methods as the embryos remain in the incubator in a stable environment throughout the culture process without the need to remove them for daily checks.

Time-lapse incubators provide our team of embryologists additional morphological and developmental information about your embryos, including the assessment of morphology, multinucleation, cell division patterns and the time of embryo divisions – all contributing to the selection of a better quality embryo(s) to transfer.

Key Benefits of time-lapse imaging

  • Selection of “highest potential” embryos for embryo transfer giving you your optimal chance of having a baby
  • More stable environment for your embryos during culture
  • Time-lapse developmental video of your embryos for you to keep

There are scientific studies that have shown an increase in the chance of a live birth when using this technology to grow embryos. Embryologists feel that the use of these incubators improves the culture environment and helps in selecting good embryos and ignoring embryos with poor development.

Treatment add-on

Time-lapse imaging is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as amber in the HFEA traffic light system for additional treatment options as there is conflicting evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients.

Time-lapse imaging of embryos is included free of charge in all of our treatment packages (where applicable).


EmbryoGlue

EmbryoGlue is formulated to imitate the environment of the womb at the time of the implantation. It is not glue in the true sense of the word, but its function is similar to the function of glue because the aim is to increase the chance of the embryo implanting in the womb.

EmbryoGlue contains sugars and amino acids that support the embryo during the transfer and implantation period. EmbryoGlue contains hyaluronan which is a natural substance commonly found in all tissues in the human body. EmbryoGlue® is the only available product that is enriched with hyaluronan. Its concentration in the uterus at the time of implantation increases and the uterine wall and embryo contain receptors for its molecule. It is believed that hyaluronan in EmbryoGlue establishes a connection between the embryo and the uterus.

Who should use EmbryoGlue?

EmbryoGlue® is hoped to bring benefits for all patients who undergo an embryo transfer in the course of assisted reproduction. Scientific studies have shown that the use of an increased level of hyaluronan in embryo transfer media may improve the chance of implantation after the embryo transfer. In the research studies referenced on the manufacturer website, results were better than those for transfers without hyaluronan. 

Treatment add-on

EmbryoGlue (Hyaluronate enriched medium) is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as amber in the HFEA traffic light system for additional treatment options as there is conflicting evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients.

Risks

As per HFEA “Hyaluronate enriched medium does not carry any additional known risks for the person undergoing fertility treatment or the child born as a result of fertility treatment.

If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.”

Clinical Evidence

As per HFEA “There is one high quality study in this review which shows that the use of hyaluronate enriched medium may be effective at improving your chances of having a baby, other studies in the review were of moderate quality. Further high-quality studies are needed before doctors can be confident of the benefits of hyaluronate enriched medium.

At the October 2021 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for hyaluronate enriched medium. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage. This Cochrane review has further information on the evidence for hyaluronate enriched medium, which we are currently considering.”

For further information regarding this treatment add-on, please visit the HFEA website using this link.

Costs

EmbryoGlue is included free of charge in all of our treatment packages (where applicable).


Assisted Hatching

The egg and early embryo are surrounded by a thick layer of special proteins called the zona pellucida (or "zona). Before an embryo can implant in the womb it has to break out or "hatch" from its zona. Some people think that assisted hatching - using acid, lasers or other tools to thin or make a hole in this shell - may prevent the embryo from becoming stuck within it. At City Fertility, the procedure is performed using a very precise laser to create a small hole in the shell, away from the cells of the embryo. It does not reduce the chances of the embryos growing to Day 5-6 of development (the blastocyst stage) and ay "spare" embryos that make it to blastocyst stage can still be frozen if the quality is deemed suitable. 

Assisted hatching is not recommended for every patient, and we will discuss the reasosns behind offering the procedure to anyone who may fit our criteria for its recommendation. This will include those of advanced maternal age (≥40), a history of implantation failure (following one or more embryo transfers) or patients undergoing Pre-Implantation Genetic Testing (PGT), however, please see our Patient Information Sheet for the full list. 

Treatment add-on

Assisted Hatching is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as red in the HFEA traffic light system for additional treatment options as there is no evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients. For more information on this add-on, please follow the link provided. 

Risks

As per HFEA "Assisted hatching does not carry any known additional risks for the person undergoing fertility treatment. However, there is always some risk of damaging embryos with these types of procedures.

If you have any qestions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances." 

Clinical Evidence

As per HFEA "The National Institute for Clinical Excellence (NICE) is the national body advising doctors on treatments. It says "Assisted hatching is not recommended because it has not been shown to improve pregnancy rates. NICE also says that further research is needed to find out whether assisted hatching influences birth rates and to examine the consequences for children born as a result of this procedure.

Some clinics believe assisted hatching can lead to higher birth rates in specific subgroups of patients. There is however no high-quality evidence to support the use of assisted hatching for any patient. 

At the October 2019 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for assisted hatching. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage."

For further information regarding this treatment add-on, please visit the HFEA website using this link.

Costs

Assisted Hatching is included free of charge in all of our treatment packages (where applicable). 


Artificial egg activation calcium ionophore

When a sperm meets an egg, it triggers a process called egg activation which starts off the process of fertilisation and embryo development, while at the same time allowing only one sperm to fertilise the egg. If the egg does not activate, then it won’t develop.

Egg (or oocyte) activation may be stimulated by chemicals called calcium ionophores. These chemicals can be added to the liquid that the egg is placed into (culture media) in the lab.

Treatment add-on

Calcium ionophore is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as amber in the HFEA traffic light system for additional treatment options as there is conflicting evidence from randodmised controlled trials to show that this is effective at improving the chances of having a baby for most fertility patients. For more information on this HFEA add-on, please follow the link provided. 

Risks

As per HFEA "Egg activation theoretically could cause embryos to have abnormal numbers of chromosomes which would cause the pregnancy to miscarry. Currently, there is not enough evidence to decide whether these risks are a serious concern. 

Given the possible risks, clinics offering this treatment should only do so for selected patients who have had failed fertilisation and should be able to justify their reasons for doing so."

If you have any questions about the safety and risks, please discuss these with your consultant or a Senior Embryologist. They will be able to discuss the add-on with you in the context of your specific medical history and circumstances. 

Clinical Evidence

As per HFEA "In the few studies donee to date, egg activation using calcium ionophores may be effective at improving fertilisation rates in ICSI cycles where the egg and sperm have failed to activate in previous treatment cycles. However, there are no RCTs to show that it is effective and there are no follow up studies on the safety of this technique. 

At the October 2019 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence based for egg activation. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage."

For further information regarding this treatment add-on, please visit the HFEA website using this link.

Costs

Cost of this laboratory method is chargeable on top of your treatment fee.

  • Artificial egg activation calcium ionophore costs


Elective Freeze All cycles

At City Fertility we offer elective freeze all cycles to patients with high risk of OHSS and on the other end also the patients with low ovarian reserve to give a better chance of success.

Elective embryo freezing is also undertaken for fertility preservation by couples not ready to start a family in near future or someone undergoing medical treatment which may affect their fertility.

Elective freeze all cycles means that no embryo is transferred in a cycle in which the eggs are collected, and embryos created (fresh cycle). All the good quality embryos are frozen at blastocyst stage and subsequently 1 or 2 embryos are thawed and transferred a month or two later.

For patients with low ovarian reserve the aim is to batch embryos from two or more stimulation cycles comparable to what someone with normal reserve would produce in a single cycle. The embryo transfer is then performed in a frozen embryo replacement cycle. This may also leave excess embryo/embryos in storage to be used in the future, particularly beneficial for a patient with low ovarian reserve.

Treatment add-on

Elective Freeze All Cycles is outlined as an additional treatment option by the Human Fertilisation and Embryology Authority (HFEA) and has currently been deemed as amber in the HFEA traffic light system for additional treatment options as there is conflicting evidence from randomised controlled trials to show that it is effective at improving the changes of having a baby for most fertility patients. For more information on this add-on, please follow the link provided.

Risks

From the HFEA “Elective freeze all cycles do not carry any known risks for the person undergoing fertility treatment. However, there’s always a risk that one or more embryos may not survive.

If you have any questions about the safety and risks, your clinic will be able to discuss whether a treatment add-on would be safe for you to use considering your specific medical history and circumstances.”

Clinical Evidence

From the HFEA “Research into freeze all cycles is progressing quickly. There is some evidence that the body’s hormonal response to fertility drugs can affect the lining of the womb, which makes it more difficult for the embryos to implant. Freezing the embryos means they can be transferred back into the patient when the womb lining is well developed.

There is also evidence that while the birthweight of babies born from normal fresh IVF cycles is lower, from FET cycles it is higher, closer to naturally conceived babies. Since birthweight is associated with risk of disease in later life, freeze all cycles may be safer for the baby.

Some research suggests that the chances of having a baby are increased by using frozen embryo transfers (FETs) rather than fresh transfers. Currently, doctors don’t know with enough confidence whether freeze all cycles are more effective than conventional IVF or ICSI at increasing your chances of having a baby. However, there is no evidence that freeze all cycles decrease your chances of having a baby.

At the October 2021 Scientific and Clinical Advances Advisory Committee (SCAAC) meeting the Committee evaluated the evidence base for elective freeze all cycles. Minutes of this discussion and the evidence used to inform this discussion are available on the SCAAC webpage.

For further information regarding this treatment add-on, please visit the HFEA website using this link.

The use of Freeze All cycles

From the HFEA “Add-ons may be offered for reasons other than to improve the chances of having a baby and in some specific circumstances there may be a justifiable medical reason for using the add-on as part of fertility treatment. Freeze all cycles are proven to be effective at reducing ovarian hyperstimulation syndrome (OHSS). Therefore, it could be used appropriately for specific clinical cases after careful discussion with a clinician.”

Costs

To understand the costs, please refer to the price list on our website and the appropriate Costed Treatment Plan (CTP) available to download online. 

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