What is recurrent implantation failure?
Recurrent implantation failure refers to cases in which women have had three failed in vitro fertilization attempts with good quality embryos. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors. There are multiple risk factors for recurrent implantation failure, including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Recurrent implantation failure (RIF) is only applicable to patients undergoing assisted reproductive methods such as IVF.
What are the investigations and treatments for implantation failure?
Maternal blood tests
Clotting:
Implantation failure happens because blood vessels between the endometrium and the embryo are obstructed. Thrombophilia is defined as any circumstance entailing an increased risk of thrombosis. As such, thrombophilia could potentially be a contributing factor. This can be treated by aspirin or heparin injections to thin the blood.
Immune screen
Increased natural killer cells in the uterus and autoantibodies have also been suggested as a cause for the repeated failure of cycles. With the use of steroids, intralipids and other drugs to suppress the immune system, one can attain pregnancy. However, these could have side effects for both a mother and her developing baby.
Endometrial tests
Hysteroscopy or endometrial scratch
An endometrial scratch is a procedure proposed to improve endometrial receptivity and increase the probability of pregnancy in women undergoing IVF. It is generally only used for patients who have experienced multiple unsuccessful IVF cycles, despite the transfer of good quality embryos.
Endometrial Receptivity Array
The ERA test evaluates the functioning of the genes that determine the receptivity of the endometrium. The endometrium refers to the inner uterine lining to which the embryo must attach itself after fertilization. A tissue sample of the uterine lining is taken through a biopsy and the genes within it are analysed. This can then predict whether the uterus would be receptive to an embryo on the day that the embryo would have been transferred.
Paternal factors
Sperm DNA fragmentation
Sperm DNA fragmentation is a term used to denote abnormal genetic material within the sperm, which in turn may lead to male subfertility, IVF failure and miscarriage. A conventional semen analysis done for sperm concentration, motility analysis and morphology assessment cannot assess the sperm at the molecular level and as a result aid the detection of DNA fragmentation.
Embryo factors
Genetic screening
Pre-Implantation Genetic Diagnosis involves testing an embryo before it implants for a specific, known genetic disorder. Pre-Implantation Genetic Diagnosis is used so that embryos unaffected by the disorder can be returned to the uterus. Pre-Implantation Genetic Diagnosis is prescribed for someone who has or is a carrier of a known genetic disorder. While a Pre-Implantation Genetic Screening may be recommended for someone with recurrent miscarriage, someone who is older or whose ovaries do not work as well as expected, or someone with multiple failed fertility treatments.
Embryoscope™ (Time-lapse imaging)
Time-lapse imaging allows doctors to see the development of the embryo as a continuum instead of just looking at still images. This allows the doctors to assess more subtle changes seen during embryo development and identify the best embryos for transfer.
Laser-assisted hatching
Assisted hatching is often required to overcome the various hurdles in the natural hatching process and thereby increase the chances of pregnancy. Given that during IVF, the fertilization takes place in a lab, one must understand that this alone does not constitute a positive pregnancy. The embryo fertilized in the laboratory ought to be successfully transferred and implanted into the uterus. And the implantation ought to happen naturally for the eventual detection of pregnancy.
Why does implantation failure in IVF happen?
There are various biological reasons why implantation failure happens in IVF. For successful implantation, the embryo ought to be at the right developmental stage and the uterus must provide a hospitable environment. However, there are various causes that may lead to implantation failure and it will require – anatomic assessment, uterine environment testing, testing for blood clotting and genetic testing, to comprehensively identify the reason for implantation failure.
What is implantation failure in IVF?
Implantation is the stage wherein the embryo attaches to the uterine wall and is vital for positive detection of pregnancy. For successful implantation, the embryo ought to be at the right developmental stage and the uterus must provide a hospitable environment. Implantation failure is one of the common causes associated with infertility, especially in assisted-reproductive methods.
Which is the culprit – the seed or the soil?
The success of implantation various factors ought to come together at the right developmental stage with the uterus also providing a hospitable environment. However, there are various causes that may lead to implantation failure and it will require – anatomic assessment, uterine environment testing, testing for blood clotting and genetic testing, to comprehensively implantation failure.
How does embryo quality impact successful implantation?
Many factors affect the success of an IVF cycle, but embryo quality may be the most important. The majority of all failures, about 60 percent, are caused by abnormalities in the embryo. In a natural pregnancy, sperm fertilizes an egg as it travels down the fallopian tube. The cells in the fertilized egg divide and grow into an embryo as it moves to the uterus, and it implants in the uterus to continue growing.
In an IVF cycle, fertilization and embryo development takes place in the embryology lab. The eggs and sperm are combined, and the fertilized eggs begin the process of dividing and growing. The embryologists monitor the embryos and, prior to choosing which ones to transfer at the cleavage or blastocyst stage, grade them to determine which ones have the best chance of being healthy and resulting in a successful pregnancy.
What is the Role of endometrium in embryo implantation?
For successful implantation, the embryo ought to be at the right developmental stage and the uterus must provide a hospitable environment. Increased hormone levels, particularly progesterone related to fertility treatment, can create what is known as an inhospitable uterus for an embryo to implant. Other medical issues, such as polyps, scar tissue, and endometriosis, can create hostile environments for an embryo
Why might you have a “non-receptive” uterus?
There are several factors that can cause the uterus to be non-receptive to the implantation of the embryo, these include:
- Adhesions, polyps, or fibroids in the cavity
- Premature increase in progesterone levels
- Non-receptive uterine lining
- Infections of the uterus
Can implantation failure be treated? What evidence-based therapies are available?
Yes. Implantation failure is a treatment condition, should the cause associated with the failure be clearly identified. And currently, genetic factors are the most common, evidence-based causes of implantation failure. Once an abnormality associated with implantation failure is recognized, treatment options should be considered to include uterine septectomy, removal of intra-uterine adhesions, endometrial polypectomy or myomectomy and excision of hydrosalpinx.
What kinds of “non-evidence” based therapies are available to treat implantation failure?
Some of the speculative therapies that can be used for the treatment of implantation failure include:
- Use of blood thinners
- Causing a localized injury to the endometrium to improve blood flow
- Use of steroidal drugs
- Use of embryonic glue
- Co-culture of embryos with endometrial epithelial cells
- Administering Peripheral Blood Mononuclear Cell by intrauterine methods
