A glance into the world of Clinical Embryology

Let’s start at the beginning; what is infertility?

Infertility means not being able to conceive a child. Many people face problems with conception, this can be attributed to a number of contributing factors, but not all can be diagnosed. In 25-30% of cases a cause cannot be identified even after the most thorough investigations. This is due to the fact that some of the factors cannot be assessed. Common causes of infertility include problems with ovulation (whereby the body does not release eggs naturally), issues with the tubes, or for male partners this would include problems with the quality or ability of the sperm. For these issues there is a range of treatments that are offered through the assisted reproductive pathway.

Clinical Embryologists specialise in the advanced and complex diagnostic, clinical and therapeutic treatments and equipment to help people make babies via a variety of methods. Treatments performed by Embryologists and Doctors at Guy’s Assisted Conception Unit (ACU) include:

• Intrauterine insemination (IUI) – This is the least invasive and technically easiest form of treatment. In an intrauterine insemination cycle, a sample of mobile sperm is prepared by the embryologist and placed directly inside the uterus using a very fine catheter. The sperm is deposited before the release of an egg or eggs in a natural or stimulated cycle. Conception occurs naturally inside the body. IUI is usually the first step in treating couples with unexplained infertility.
• In vitro fertilization (IVF) – This involves the male’s sperm being put in with the female’s eggs in the laboratory to produce embryos. The sperm is injected into a dish containing the female’s eggs. The sperm are then able to swim and fertilise an egg in the dish.
• Intracytoplasmic sperm injection (ICSI) – is used when the sperm quality is suboptimal. This is a highly technical procedure where by a single sperm is injected into the centre of an egg to achieve fertilisation. The difference between the two is that in an ICSI cycle, mature eggs are directly injected with sperm instead of being placed together in a dish.

To understand the clinical procedures that are carried out on a day to day basis by embryologists, it is best to talk through a patient’s treatment cycle. Firstly embryologists gather eggs from the female during an ‘egg collection’. This involves eggs being removed from fluid filled follicles inside the woman’s ovaries using a needle. Each follicle is aspirated and the fluid is passed to the embryologist who searches for the eggs and places them in culture media. Once all the follicles have been aspirated and all eggs retrieved they are passed into the lab where the dish is kept in a specialised incubator that carefully controls environmental conditions. Meanwhile the male will produce a semen sample that is received in the Andrology lab to be prepared for treatment. As semen is composed of both seminal fluid and the sperm itself a sample needs to be washed. This is because the seminal fluid will inhibit fertilisation so is removed during washing. First of all samples are put on a gradient and centrifuged which separates the seminal fluid, abnormal sperm and other debris from the motile sperm suitable for use in treatment. The pellet of motile sperm is then washed and centrifuged in culture media to again remove the density gradient media and any remaining contaminants. The prepared sperm sample is then passed into the lab where it will meet the eggs! After a woman’s eggs are collected and the man’s sperm is prepared embryologists will discuss with patients the outcome of these procedures and the next steps of the treatment. This conversation is usually just to finalise the treatment plan the couple have already discussed with their doctor but changes may need to be made if the egg number or sperm quality is not what was expected on the day. Either IVF is then performed with the sperm being injected into the same dish as the eggs or ICSI when an individual sperm is injected into an egg. Fertilisation will then hopefully happen!

The eggs and sperm are left overnight in special incubators and evidence of fertilisation is seen the following morning with two pronuclei present, one from mum and one from dad. When we see this we know the embryo has been fertilised normally and hopefully a patient has a few embryos or more. We are now able to ring the patient and give them the (hopefully) good news. Waiting for this telephone call is very nerve racking and embryologists know this and try to make sure the information they give patients is clear and concise. We tell them the number of embryos that have fertilised and when the patient should be coming back to the department for an embryo transfer. The day of embryo transfer can be different depending on many factors including the number of embryos fertilised, the quality of the embryos and the age of the woman are all taken into account. Most women have a transfer on Day 5 of embryo development when the embryo has reached a particular milestone of becoming a Blastocyst. If women have more than one embryo or are not having a fresh transfer they will have embryos frozen for later cycles. Freezing happens on Day 5 or 6 of development usually. We can’t just stick embryos in a freezer, we have to use special freezing media and a protocol that slowly removes water from inside the embryo to make sure that when frozen, ice doesn’t form and cause damage. Embryos, once frozen, are stored in Liquid Nitrogen at a chilly -196°C. This is in storage tanks called Dewars. A patient can have eggs, sperm and embryos all frozen and stored for future use. Storage of eggs and sperm for patients who which to preserve their fertility is common.

Fertility Preservation can be for those being treated for cancer, men/women who are not yet ready to have a family, those in the armed forces or transgender persons beginning hormone therapy or reconstructive surgery. Freezing of tissue from the ovaries or testicles is also possible. For women this is usually cancer patients either younger girls who haven’t begun ovulating or for women who cannot produce mature eggs. For men, tissue freezing occurs when viable sperm are not found in the ejaculate, a condition known as azoospermia. Surgical Sperm Retrieval techniques also exist for other male fertility issues. When a man is unable to produce a sample by ejaculation, he has azoospermia caused by a blockage or lack of mature sperm being produced in the ejaculate. The procedures for sperm retrieval usually involve sperm being aspirated from the testicle or a small portion of testicular tissue being removed during surgery. The embryologist will then search for sperm in the sample and if any is present, it is either used for treatment that day or is frozen.

A service offered at Guy’s ACU for families who are at risk of having a child with a specific genetic or chromosome disorder is Preimplantation Genetic Diagnosis (PGD). PGD is a branch of treatment that is able to check the genes or chromosomes of embryos created in the lab for disorders. As embryologists, we perform a biopsy of the embryos that have reached day 5-6, like when we usually transfer embryos or freeze them. The biopsy involves taking a few cells from a specific region in the embryo called the trophectoderm. These cells are what later develop into the placenta. The removal of the cells is carried out on a special inverted microscope, the same that is used for ICSI procedure. A laser is used to create a tiny hole in the outer coating of the embryo and then a specialised pipette is used to retrieve a few cells from the trophectoderm layer. This process sounds like it would cause damage to the embryo but it is very safe especially as the cell layer that becomes the foetus is not touched during the procedure. The embryos will now be frozen to await the results of genetic testing. The Genetic testing is carried out in genetic laboratories at Guy’s ACU.

We are lucky to have all the testing in-house and due to the success of our unit we are sent embryos for PGD from clinics across the UK. The results of the genetic testing reveals which of the embryos is unaffected or affected by the disorder that was being tested for. If unaffected embryos are available, these can be transferred into the womb to hopefully make a healthy baby.