Repeated implantation failure (RIF) or Recurrent IVF failure is considered when embryos transferred to the uterus, fail to implant following several In vitro fertilization (IVF) treatment cycles. Though, there is no formal criteria defining the number of failed cycles or the total number of embryos transferred in these IVF attempts. However, we recommend defining RIF as failure of implantation in at least 4-5 consecutive IVF attempts, in which 1–2 embryos of high grade quality are transferred in each cycle. The causes of RIF may be varied and may involve any of the following factors:
- the egg,
- the sperm,
- the embryos created,
- the uterus,
- maternal and paternal health, or
- combination of any of the above listed factors.
The Egg: The quality of a woman’s eggs plays an important role in creating a healthy embryo. As maternal age advances, the percentage of chromosomally abnormal eggs (aneuploidy) increases, reducing the chance of creating a healthy embryo naturally. There are several solutions to counter this concern – Egg freezing technology can be opted for preserving the healthier eggs available before a woman attains 35 years of age; else stimulating drugs can be used to obtain more eggs to help develop more embryos and with Pre-genetic screening technology (PGS) the healthiest embryos can be identified for implantation; egg donation can also be considered as an option.
The Sperm: The sperm plays an equally important role in the formation of a healthy embryo, by transmitting a healthy DNA to the egg. In some men, the sperm functions – concentration, motility or morphology may be poor; or the DNA may be damaged. This could be attributed to advancing age or lifestyle disorders – smoking, drinking, obesity, stress etc. Computer Aided Semen Analysis (CASA) is a test performed to screen for male fertility problems. Treatments to improve sperm quality include suggested use of antioxidants such as zinc along with making lifestyle changes. Intracytoplasmic sperm injection [ICSI] is a technology used for fertilising an egg with a chosen quality sperm to help develop high quality embryos and correspondingly improve the implantation success rate per cycle. Donor sperm can also be considered as an option.
The Embryo: An embryo that contains a normal number of chromosomes i.e. 23 pairs of chromosomes in each cell, is called a ‘euploid’ embryo. An embryo that carries an abnormal number of chromosomes is ‘aneuploid’. Examples of aneuploid embryos include those with 18 sets or 21 sets of chromosomes, or maybe a single additional or missing chromosome resulting in a total of 47 or 45 chromosomes instead of the usual 46. There are high chances of the uterus rejecting an abnormal embryo resulting in an implantation failure. Pre-genetic Diagnosis (PGD) and Pre-genetic Screening (PGS) technologies can be used to identify healthiest embryos for implantation.
The Uterus: A successful implantation depends on the embryo quality as well as a receptive endometrial environment. The uterus may be affected by either structural, hormonal or immunological conditions which may be the reason behind the repeated implantation failures:
- Adenomyosis endometriosis,
- Intrauterine adhesions,
- Abnormal uterine shape,
- Difficult cervix affecting embryo transfer,
- Early rise in progesterone prior to egg collection in an IVF cycle,
- Natural killer cells / immune system.
Treatment for all the above listed conditions is very much possible and can be opted for once the actual cause of RIF is identified.
In addition to the above, general maternal – paternal health concerns could also be a reason behind recurrent implantation failures. Lifestyle diseases – obesity, stress, excessive smoking or alcohol intake, improper work-life balance, unhealthy diet and physical inactivity are some common factors that both the partners need to take care of when planning to start a family.
Certain other maternal health factors affecting recurrent implantation failure include:
- Systemic diseases such as diabetes,
- Antiphospholipid syndrome i.e. autoimmune and blood clotting disorders,
- An elevated level of Natural Killer cells (immune cells that are particularly prominent in the uterus around implantation) in either the blood or the uterus,
- Thyroid dysfunction – both hyper and hypothyroidism,
Most importantly, STRESS – both physical and emotional, is a natural part of assisted reproductive treatments and its impact on IVF cycle success rate is difficult to measure. Hence it is important for the partners/individuals to do whatever will help put them in the best physical and emotional frame of mind during the course of the treatment – take regular counselling sessions, make lifestyle changes, surround themselves with loving and supporting family and friends, meditate – basically stay happy, healthy and positive.