IVF Failures and Further TestingOne of the most depressing situations an IVF patient can experience is a negative pregnancy test after going through a stressful period of treatment. An IVF treatment is a financial and an emotional investment, and if it results in a negative outcome, there is a period of intense emotions. While the aim of any fertility treatment is to obtain a positive result, it is also important to accept that some treatments may fail. When faced with a failure, it is easy to get lost in emotions and have overwhelming negative thoughts. However, one important thing to keep in mind is that sometimes, after a failed IVF cycle, it might be possible to find clues that will lead to a more effective treatment later on. While infertility testing provides a very good picture of your fertility status, it may not always successfully predict how your ovaries will respond to certain medication or how the quality of the eggs will turn out. A failed IVF cycle, while depressing, can provide extremely useful information to your IVF specialist such as your ovarian response, egg quality, fertilization rates and embryo quality. Based on these observed characteristics, a future cycle can be more thoroughly planned in an attempt to correct problem(s) that could explain why your treatment may have failed.
After a failed IVF cycle, it will be important for your IVF specialist to go over your file and correlate previous test results with the details of the failed cycle. It will be essential to see if measured cycle outcomes were in line with pre-cycle infertility assessment. If pre-cycle expectations were not met with the measured cycle outcomes (such as number of eggs, quality of eggs, quality of sperm, fertilization rates, cleavage embryo formation rates, blastocyst embryo formation rates), your IVF specialist may ask for additional tests in order to be able to explain the discrepancy. Sometimes, the outcome may not correlate with expectations not because of another problem, but simply because your ovaries may respond slower than average. In any case, it is important to revise your cycle details carefully in order to derive a conclusion that will help improve your chances of success on the next attempt.
We have had patients achieve pregnancy on their very first IVF cycle and we have seen patients achieve a pregnancy on their fifth cycle! While it is nerve-wrecking to go through one failed IVF cycle after another, this is a very unique and personal experience for each and every patient and no two patient experience is likely to be identical. Let’s understand how an IVF cycle may fail and what can be done differently after a failed cycle.
In such cases, when the problem is with egg count or quality, the treatment protocol can be modified and a more aggressive approach can be adopted to maximize ovarian response. Depending on the patient’s age bracket, ovarian function and the nature of the specific problem, different approaches can include:
– Changing the dose of medication in an attempt to increase the number of eggs to be obtained on a subsequent cycle. If the ovarian response has been less than anticipated, then a higher dose of ovarian stimulation medication can be administered.
– Changing the ovarian hyperstimulation protocol altogether. Sometimes, in women with low ovarian reserves, using a long agonist protocol may suppress the ovaries more than anticipated, and reduce the response to ovarian stimulation with gonadotropins. To avoid this, it might make sense to switch to an antagonist protocol where there is no down-regulation. (To read more about different IVF protocols and how they work, please refer to choosing the right treatment method page of our website).
– Considering alternative treatment modalities. If the ovarian reserves are highly depleted and changing the medication dosage or the protocol are not likely to result in more favorable outcomes, different treatment approaches can be considered. These may include:
Ovarian PRP Treatment: Where the patient’s ovaries are injected with her own PRP in order to stimulate the stem cell line and initiate cellular regeneration. While still explored at a trial basis, we have achieved success with many patients using ovarian PRP application.
Using Cytoplasmic IVF Transfer: Where an egg donor is used for her egg’s cytoplasm. Young and healthy cytoplasm coming from a young egg donor can provide a better host for the patient’s own eggs and allow for improved fertilization rates.
Using donor eggs: If patients have been through a number of failed cycles and they do not want to lose time with experimental treatments, then the next best alternative would be to opt for donor eggs.
When the problem lies on the side of sperm, supplementary medication can be used to aid with spermatogenesis. In total azoospermia, then surgical sperm extraction methods can be a solution if azoospermia has been diagnosed as obstructive. In case of non-obstructive azoospermia, our clinic uses stem cell regenerative therapy as a clinical trial for patients exploring further options to be able to use own sperm sample. In cases where patients decide to use a sperm donor, we are able to offer donor sperm during their IVF cycles.
Total fertilization failure: None of the eggs are fertilized by the sperm sample and there are no available embryos for an embryo transfer. While this is rather a rare phenomenon, it can be caused by sperm or egg related problems. A total fertilization failure (TFF) will lead to a canceled cycle. TFF in one IVF cycle may not necessarily mean the next cycle will have a similar result. However, it is important to understand why the eggs may not have fertilized with the sperm sample. In most cases, a TFF is attributed to either the oocytes or the sperm cells. One of the most common cases where TFF is observed is when using poor quality immature sperm cells obtained via surgical sperm extraction methods when the male partner suffers from obstructive azoospermia.
Failed Implantation: Despite having normal oocyte and sperm parameters, some patients may undergo many IVF cycles yet without a positive outcome. This is usually labeled as “unexplained infertility”. When dealing with unexplained infertility, certain additional testing will be in order in order to understand if additional precautionary measures during IVF treatment may help increase the chance of implantation.
The usual suspects behind IVF failures are often the eggs and the sperm. These are the first things that come to mind when an IVF specialist looks for a reason behind a failed cycle. Commenting on egg and sperm quality is relatively easier compared to many other factors since there are extensive tests that can be administered to detect egg and sperm related problems. If a patient has undergone a number of IVF attempts and standard testing indicates normal parameters, then the next step will be to undergo a series of advanced infertility testing. These include:
– A karyotype analaysis, which is a chromosomal analysis of the male and the female patient to detect any possible genetic problems. There are chromosomal defects that may not exhibit any symptoms, and won’t be evident until a karyotype analysis has been performed. Most common chromosomal problems that can impair a person’s ability to reproduce without any symptoms present are reciprocal translocations. If this is the case, Pre-Implantation Genetic Screening for the embryos will often solve the problem and allow patients to have a healthy child.
– Advanced semen testing (if there is enough reason to believe that failed embryo development or the implantation failure can be attributed to sperm DNA problems). Now, North Cyprus IVF Centre is one of the very few clinics in the world which can offer sperm separation based on DNA integrity through a breakthrough discovery called the “MicroFluidic Chip“.
– Advanced uterine testing to detect possible problems with the uterus that may not be visible during a standard trans-vaginal ultrasound scan. This may include a hysteroscopy or a hysterosalpingography (HSG). Research and clinical evidence indicate that endometrial receptivity can be assisted via the use of chemical messengers. At North Cyprus IVF Center, we use Neupogen, a recombinant of Granulocyte Colony Stimulating Factor (G-CSF). Research and clinical work have provided significant evidence that viable embryos and healthier placenta express higher levels of G-CSF and this higher level has been associated with improved embryo implantation and higher IVF success. The use of neupogen as an endometrial wash and a sub-Q injection at certain time intervals during an IVF cycle have shown a dramatic improvement in both endometrial receptivity and ongoing pregnancy rates. In our own practice, we have observed similar outcomes and we have incorporated neupogen as part of all patients with repeated IVF failures.
Other possible considerations can be listed as follows:
The inside of the uterine cavity is normally considered to be a sterile environment. It has been strongly suspected that infection of the uterine cavity with bacteria may cause an inhospitable environment that would lead to failure of embryos to implant. In cases where there is a reason to suspect a uterine infection, an endometrial biopsy procedure may be called for in order to make an effective assessment. Normally, infections can be treated with antibiotic use. There are also other infectious diseases that can be considered during this investigation such as CMV IgG, Chlamydia and more.
Immune factors as a cause for IVF implantation failure
The immune system is designed to protect individuals from infection with microorganisms and to fight off abnormal processes in the body like cancer. In the areas of IVF, infertility and recurrent pregnancy loss, there has been an extensive amount of investigation as to the role of immune factors in the implantation process of the embryos. In some cases, the immune system is believed to see the embryo as a foreign object and reject its implantation.
Thrombophilias are conditions that result in an increased chance for blood clotting. There have been many studies showing an association between the presence of thrombophilias in women and the risk for miscarriage. Some studies also indicate that thrombophilias can also be associated with implantation failures. Thorombophilia is a condition creating a hypercoaguable state which leads to thrombosis (blood clotting) at the site of embryo implantation, cauusing an implantation failure.
This is not a comprehensive list of what might be causing your IVF failures, however, they are the main contributing factors. For a better assessment, your case will need to be analyzed with all aspects included because each patient will necessitate a different approach.
Please contact us for more information, using the contact form either on this page or on our contact page.