During an IVF cycle, an embryo grown in the lab is placed into a woman’s uterus (womb) – a process called embryo transfer. If the embryo successfully attaches to the wall of the uterus (known as implantation) and continues to grow and develop, a pregnancy results. Sometimes, however, embryos fail to implant. If this happens during three or more IVF cycles, it is referred to as ‘repeated implantation failure’. While this can be a frustrating hurdle for women and couples undergoing IVF, there are ways to improve the success of embryo transfer depending on the likely cause of implantation failure.
Factors relating to either one or both parents can contribute to repeated implantation failure, so a range of tests are typically used to help investigate and determine the cause.
A high-quality egg and sperm are essential ingredients for a healthy embryo. Bearing in mind that healthy embryos have the best chance of implanting in the womb, it is important to use eggs and sperm of the highest quality possible during IVF. Unfortunately, numerous factors can reduce egg and sperm quality.
Age plays a major role in egg quality (and quantity). Once a woman reaches the age of 35, egg quality typically declines. This means that eggs collected from older women are less likely to successfully implant in the wall of the womb.
Sperm defects can also contribute to recurrent implantation failure. For instance, damage to the sperm’s genetic material – also known as DNA fragmentation – can affect the development of an embryo and, therefore, the likelihood of implantation. Aging and lifestyle factors like smoking, alcohol consumption and being overweight, as well as some underlying medical conditions and prescription medications, can damage the DNA in both sperm and eggs. While there isn’t a test to assess egg quality, doctors can look for higher than normal levels of sperm DNA fragmentation when performing a semen analysis.
Variations to the chromosomes inside the embryo are a major cause of recurrent implantation failure. Chromosomes are special structures, found within cells, that contain DNA. Normally, each egg and sperm contain 23 DNA-housing chromosomes, and during fertilization all 23 are passed on from each parent (giving the embryo a total of 46 chromosomes).
However, chromosomal errors can sometimes arise during the generation of an embryo. This includes abnormalities in the number of chromosomes present (known as aneuploidy) and structural changes affecting the size of chromosomes or how the DNA is organized within them. There can also be an increase in the amount of genetic material present in the embryo. No matter the type of error, chromosomal anomalies within the embryo are much less likely to result in an ongoing pregnancy.
Female age is the biggest contributing factor to chromosomal anomalies in the embryo. However, rarely a person can be born with a structural rearrangement in their own chromosomes, which can predispose them to producing mostly abnormal eggs or sperm. This can be detected by performing a karyotype test on the individuals providing the egg and sperm. If doctors suspect chromosomal error, they can use pre-implantation genetic testing (PGT-A or PGT-SR) before transfer to assess an embryo’s chromosomal arrangement.
For an embryo to successfully implant in the uterus, the endometrium (the tissue that grows on the internal lining of the uterus) must undergo biological changes. In preparation for a healthy embryo, the endometrium thickens and becomes responsive to potential implantation by the embryo.
A number of conditions that cause inflammation and scarring, such as fibroids, polyps, adenomyosis, hydrosalpinges and endometriosis, can impact the structure of the uterine environment. Sometimes, the presence of these conditions can make it more difficult for the embryo to implant in the wall of the uterus.
Imaging studies and surgical tests can help us determine if an inflammatory condition is affecting the uterine environment. These include pelvic ultrasound, as well as the insertion of a camera via hysteroscopy or laparoscopy.
Health and lifestyle factors relating to one or both parents can impact the success of embryo transfer. In the mother, underlying health conditions, such as diabetes, thyroid disease and other endocrine disorders, as well as autoimmune disorders and clotting disorders (e.g., thrombophilia), can block the interaction between the embryo and the endometrium. In addition, alcohol consumption, smoking and other modifiable lifestyle factors in both parents (including poor diet, exercise and being overweight) may also contribute to recurrent implantation failure by affecting egg/sperm quality and the health of the uterine environment.
To improve the chances of the embryo implanting in the wall of the uterus, an embryo transfer method is designed to both protect the embryo and help it reach its destination. A gentle tube called a catheter provides a pathway for the embryo from the incubator to the uterus. Along the way, ultrasound imaging is used to make sure that the placement of the embryo is precise.
Before transfer, embryo can also be put in a special substance called EmbryoGlue to boost the chances of it implanting in the uterus. EmbryoGlue contains a compound normally found in the uterus called hyaluronan that may help the embryo attach to the wall of the uterus.
If embryo transfer fails several times, it’s typically recommended to test for some of the common causes discussed above and may also recommend some additional treatments, described below.
IMSI (short for Intracytoplasmic Morphologically selected Sperm Injection) is a technique that is used to help select a sperm for ICSI (or IntraCytoplasmic Sperm Injection). ICSI may be used during IVF to aid fertilization. During ICSI a single sperm is isolated and injected into the center of a mature egg, helping to overcome any barriers to natural fertilization. In the case of IMSI, doctors first look at all the available sperm under a powerful microscope, then pick the sperm with the healthiest-looking shape and structure to introduce into the egg via ICSI.
Hyaluronic acid (HA) ICSI, also known as PICSI (Physiological Intracytoplasmic Sperm Injection) is another technique sometimes used to help select the best sperm for the ICSI procedure. Sperm that can bind to hyaluronic acid (a substance found naturally in your body) have low levels of DNA fragmentation. Choosing the best sperm increases the chances of a healthy embryo, which in turn, has a higher chance of implanting.
Before transfer, your doctor can also assess your embryos for chromosomal or specific genetic defects using pre-implantation genetic testing (PGT). This may include PGT-A to screen for random chromosomal anomalies (e.g. due to age), or PGT-SR to detect structural rearrangements in the chromosomes inherited from the sperm or eggs. This assists us in choosing embryos for transfer that have the best chance of implanting and resulting in an ongoing pregnancy.
As mentioned above, a favorable uterine environment helps implantation to take place. Depending on the cause, location and severity of the inflammation, surgical treatments targeting conditions that impact the structure of the uterus may be useful. For example, laparoscopic surgery is frequently used in women with endometriosis and can help remove scar tissue and/or growths.
Iranian surgery is an online medical tourism platform where you can find the best doctors and fertility specialists in Iran. The price of IVF in Iran can vary according to each individual’s case and will be determined by an in-person assessment with the doctor.
For more information about the cost of IVF in Iran and to schedule an appointment in advance, you can contact Iranian Surgery consultants via WhatsApp number 0098 901 929 0946. This service is completely free.