Why IVF with donor eggs may fail sometimes? Factors that impact the outcome

Egg donation is not the magic bullet we would like it to be. Like it or not, like every medical treatment, it carries a risk of failure. Despite its many advantages, it can not provide a 100% guarantee of success.

But what can cause an egg donation cycle to fail? To help us understand all the different factors that can impact a donation treatment’s outcome, we asked Dr Natalia Szlarb, Gynaecologist & Fertility Specialist.

First, why is egg donation so effective? Well, as a result of a sociocultural shift in the 1960s, it is now common for women to delay pregnancy and childbirth in favour of getting an education or establishing a career. As such, it is now more common for women to become mothers in their late thirties or even forties. The problem, however, is that our bodies weren’t designed with that in mind. Women have a limited reproductive capability that decreases with age. As we get older, the eggs we produce have a higher chance of containing genetic defects. If fertilised, the resulting embryo carries these defects, which significantly increases the risk of implantation failure, miscarriage, or congenital disorders such as Down syndrome.

Sometimes we start thinking about creating our family when we passed our fertility peak; although the precise cut-off point is different for every woman, research suggests that fertility starts dropping significantly after the age of 35. Implantation, pregnancy and live birth rates all drop significantly with the age of the patient. Unless you had the forethought to freeze your own eggs when you were younger, you may find yourself in a situation in which achieving pregnancy using your own eggs may be difficult, if not impossible.

Egg donation vs. own eggs IVF

This is where egg donation comes in. By providing oocytes from healthy, young donors, all of the issues stemming from advanced maternal age are bypassed. Unlike own egg treatments, IVF using donor eggs remains effective no matter how old the patient is. So where’s the catch?

Well, there aren’t any ‘perfect’ donors. Like it or not, no matter how young or healthy you are, once you undergo hormonal stimulation, only about half of the eggs retrieved from you will be euploid – that is, contain a normal number of chromosomes. This ratio will drop with age – from around 50% before the age of 35 to around 11% past the age of 42. Egg donors usually manage a 61% euploidy rate in embryos created from their eggs – which means that for every ten eggs collected, around six of them will result in genetically correct embryos.

Is the PGS / PGT-A a solution for IVF failure?

How do we know which embryos are genetically correct? We test them through a biopsy – embryologists develop an embryo until day five, when they reach the blastocyst stage. During this stage, an embryo consists of over 200 cells. A small sample – about five cells – is collected from the trophectoderm, the part of the embryo which will later develop into the placenta. This sample will then be used to determine whether or not the embryo is euploid or not.

This type of testing is called PGT-A, although until recently it was also known under the name PGS. Although widely used, it is still not yet widely available as a standard treatment in IVF. There are, however, increasing number of experts who believe it will become more widely applied as the advantages of PGT-A are numerous. By selecting the correct embryo, the chances of achieving a successful pregnancy skyrocket, while the risk of miscarriage or implantation failure drops significantly.

IVF failure and donor matching process

The donor matching process also has an impact on embryo creation. Patients from certain genetic groups – for instance, some African-American populations – can have a higher risk of carrying genetic disorders such as sickle-cell disease. Through genetic testing during the donor matching process, the possibility of creating an embryo which could carry or suffer from such a disorder can be eliminated almost entirely.

Don’t let all this talk about eggs fool you – after all, you can’t make an embryo without sperm, and sperm too has an impact on the viability of the embryos. Certain tests can be performed to determine if there are any issues with sperm, be they DNA fragmentation or poor morphological parameters. Basic sperm analysis is a standard treatment at many IVF clinics, in fact.

Embryos are just one piece of the larger puzzle, however. The endometrium is the other major part of reproductive medicine, and in Dr Szlarb’s view, it has been unjustly ignored in favour of focusing on the embryos. Even if embryos undergo genetic testing, it’s not always possible to achieve pregnancy.

IVF test cycle before an embryo transfer

To address this issue, each patient undergoes a test cycle before the actual embryo transfer. During this cycle, the patient takes oral or transdermal oestrogen; on day 10 of this cycle, they undergo an ultrasound scan in order to measure the thickness of the endometrial lining. In complicated cases, especially in recurrent implantation failure, a uterus lining biopsy is performed on the 21st day of the test cycle, in addition to another scan. The sample from this biopsy is then sent for receptivity testing, which tells us about the timing of the patient’s “implantation window”, or the best possible time to transfer the embryo.

It’s not enough to transfer the embryo at the right moment – the uterus must also be free of any physical defects. A hysteroscopy can reveal polyps, myomas and fibroids, all of which can make achieving pregnancy much harder – Fortunately, most cases can be fixed with a simple surgical procedure.

IVF failure and immunology

Immunology also plays a large factor in implantation. The uterine lining is filled with cells called NK cells. Their sole purpose is to destroy anything that could endanger the endometrium – sometimes, they may attack embryos trying to implant themselves. Fortunately, immunosuppressants can help prevent this.

Other resources regarding IVF failure worth reading:

• IVF fails – is it worth keeping going?
• IVF failure – What’s next?
• Implantation failure and IVF with donor eggs