Advanced Treatments

ERA is a method of assessing when the endometrium is most receptive, in order to give a personalised embryo transfer.

The receptivity of the endometrium is a crucial factor in determining the success of IVF treatment.

The endometrium is the tissue lining the uterus, which gets thicker during the cycle until it reaches the optimum thickness for implantation following ovulation. The endometrial receptivity is the status in which the endometrium is ready for embryo implantation to take place and it is also called window of implantation. This occurs normally around days 19-21 in each menstrual cycle of a fertile woman.

In some couples who have recurrent implantation failure, it may be that the window of implantation is displaced either back or forward a few days. The ERA test involves taking a biopsy of the womb-lining and analysing the genes of this tissue taken on the day of “normal” receptivity”. The biopsy procedure is simple, fast and performed in clinic in a similar procedure to an embryo transfer.

ERA can identify certain genes that are normally active when the endometrium is receptive, and it can pinpoint these genes and check whether they are switched on or not. This gives a good idea of whether the endometrium is ‘pre-receptive’, ‘receptive’ or ‘post-receptive’. The test will be carried out in the month prior to the treatment cycle, and the results will determine the exact timing of the embryo transfer in the month of treatment.

In up to 20% of couples with repeated implantation failure this result confirms the endometrium is “non-receptive” so the window of implantation is displaced. This can allow us to personalise the day of embryo transfer and optimise the outcome and minimise further failed cycles.

Reproductive immunology: implantation failure and recurrent early pregnancy loss
Successful pregnancy requires three things: a capable embryo, a capable uterus and immune acceptance. For decades we have understood that not all embryos are capable. Genetic abnormality is the most common cause of miscarriage and implantation failure. The advice offered following the first miscarriage in women who conceive naturally is “it’s just one of those sporadic things, try again”. But when recurrent miscarriage occurs after natural conception, or for patients who undergo IVF with repeated excellent quality embryos transferred and yet have no success, other factors must play a part.

The question has been pondered for years as to the role of the immune system in successful pregnancy, but evaluation has proven to be scientifically challenging. Clinicians are divided on opinion as to the role of the immune system, and it is hard to get patients to sign up for a randomised study as all couples want a baby so are unwilling to sign up to the placebo medication!

We at Barbados Fertility Center have been testing and treating women for many years and indeed are one of the many leaders of Reproductive Immunology practice within the IVF field. We have seen hundreds of cases of repeated miscarriage or IVF failure be successfully treated with the use of immunosuppressive regimes to not test and offer treatment when indicated.

What is reproductive immunology?
Reproductive immunology is a field of medicine which studies the interaction between the immune system and reproductive organs. Research has suggested that during a normal pregnancy, a unique type of immunity occurs that stops the body rejecting an embryo as a foreign body and aids the growth and development of the foetus. If this immunity does not work properly, embryos may not implant or may be rejected early after implantation. A number of important components of the immune system have been recognised as key players to successful pregnancy.

Antibodies are molecules that are produced by white cells that can attach to cell membranes and change how the cell communicates with other cells or tissue interfaces. There are thousands of identified antibodies but the ones which are particularly associated with complications in implantation and pregnancy include: Antiphospholipid antibodies and anti-thyroid anti-bodies. The potential impact has been well documented in scientific studies for years. Testing for antibodies is a simple and readily available blood test, done by most general laboratories.

Thrombophilias; It is now recognised that a number of inherited or acquired disorders of blood clotting exist. In normal pregnancy the ability of the mother’s blood to clot in the placenta is supressed to allow flow through the fetal-maternal circulation. If a woman has an inherent increased ability to form blood clots this can affect this process and negatively affect pregnancy – implantation failure, miscarriage, pre-eclamptic toxaemia, intrauterine growth retardation and even unexplained intrauterine death have all been shown to be increased in women with thrombophilias. Tests can be done to diagnose specific thrombophilias.

What are NK cells and TNFα?
Natural Killer (NK) cells are one type of immune cell – normally circulating in blood. These express CD56 and as their name suggest have the ability to directly kill foreign or abnormal cells. Elevated levels or functionality can be harmful to the reproductive process and block successful implantation, even when the embryo is capable. They produce cytokines and specifically TNFα.

Th1 and Th2
T helper cells are present in a balance. It has been found that women with recurrent IVF failure or miscarriages have the balance of these cells shifted towards Th1. TNFα is one of the most potent cytokines released by TH1 cells.

Reproductive immunophenotype is the detailed study of white bloods cell. The majority of white cells are lymphocytes, of which there are a number of subtypes, which play different roles in the immune defense. Conventional microscopy can assess simple analysis of the numbers of certain types of white cells, for example, which are lymphocytes.  However, to assess the subtypes of lymphocytes requires specialised techniques which assess the protein molecules and categorise these further into  B and T cells and natural killer cells. This type of detailed analysis is referred to as a reproductive immunophenotype.

Our programme
All our patients are screened for the most common immunology problems such as antibodies, before starting assisted reproductive treatment. Those women at high risk of more profound immune factors such as women who have an autoimmune disease or who have a history of repeated failed IVF, recurrent implantation failure or pregnancy loss, undergo to a comprehensive investigation panel including NK cells and Immunophenotype assay. The results of the immunological panel are careful analysed and interpreted to choose the best medication and the correct dose that more efficiently addresses the defect being observed.

While not every miscarriage or IVF failure is due to an immune cause there are many cases that careful evaluation and, if necessary, treatment is the crucial factor to a successful pregnancy. Thanks to our long experience in this field, we have successfully treated hundreds of patients with positive results using a personalised therapeutic protocol with the right combination of medications, which specifically targets their underlying immune component to their infertility.

Micro-TESE is available at the Barbados Fertility Center and is now the standard for this type of procedure.

An increasing number of men seen in our practice for male infertility are azoospermic. Approximately 80 % of these men have Non-Obstructive Azoospermia (NOA).

Until recently, these men with primary testicular failure were considered “sterile”, and donor sperm insemination or adoption recommended as the only means of having a family. Several observations have changed the approach to this condition. Direct evaluation of testis biopsy specimens often demonstrates sperm in men with non-obstructive azoospermia, but not at high enough levels to yield sperm in the ejaculate.

With advances in sperm retrieval techniques, sperm can be found in nearly half of men with non-obstructive azoospermia. MicroTESE is a procedure that allows for the precise removal of tiny volumes of testicular tissue in areas of active sperm production using a microscope, improving sperm yield compared to traditional biopsy techniques. Seminiferous tubules containing sperm can often be identified under an operating microscope after opening the testis. This approach has a number of advantages over other sperm retrieval techniques. It maximizes the yield of spermatozoa while minimizing the amount of testicular tissue required and vascular injury created, by making identification blood vessels easier.

Microdissection testicular sperm retrieval is a cutting edge procedure for male infertility and probably the most important advancement of the last years in treatment of Non-Obstructive Azoospermia offering new hope. However, a cautionary note needs to be made, this procedure requires a highly skilled surgeon who has extensive experience using an operating microscope and doing testicular sperm retrievals.

We are the only Center in the Caribbean offering fresh and frozen Micro-TESE; this surgical and laboratory procedure is done through our experienced andrology staff, Katerina Arvaniti and Dr. Corona.

Testicular biopsy is used to collect sperm directly from the testis or the tubes conveying sperm from the testis. The testis might be creating sperm, which may not be present in the ejaculated semen. This may be for a number of reasons such as:

• An absence of the tubes that convey the sperms from the testis -this may due to having had a vasectomy or it can occur in patients with cystic fibrosis.
• A blockage of the tubing -this may be due to infection.

There are two common approaches to testicular biopsy:

• PESA is when a fine needle is inserted into the tubes that convey the sperm out of the testis. One area of this tubing, the epididymus, is a natural reservoir for sperm and is therefore a good place to aspirate them from.
• If a PESA is not possible or no sperm are identified then the procedure progresses onto testicular biopsy. This procedure involves the removal of very small pieces of tissue from the testis -the Embryologist then processes the biopsies with a view to finding motile sperm.

The testicular biopsy procedures are performed under local anesthetic. The procedure takes about 15 minutes.

Sperm suitable for ICSI are sometimes not found. It is prudent, therefore, to have some form of sperm as “back-up” in order that the ICSI treatment cycles not have to be abandoned.

The sperm recovered by either of these techniques is only suitable for use with ICSI. Once the ICSI has been completed and sperm remaining, of good quality, may be frozen for use with future ICSI cycles.

The success rate for ICSI is typically 30 – 55% at BFC per treatment cycle. However, the success rate is dependent on many factors, such as the age of the woman.