Repeated Implantation Failure (RIF)
What is repeated implantation failure?
Repeated implantation (RIF) failure means you have had multiple embryo transfers after IVF/ICSI with good quality embryos without resulting pregnancy.
1 ‘Good’ cleavage stage refers to ‘corresponding with the day of their development’. An embryo has four cells on day 2 after fertilisation, and 6 to 8 cells on dag three. In the CRG we only transfer day 3- or day 5-embryos.
2 On day 5 after fertilisation individual cells can no longer be distinguished, the embryo has become a blastocyst.
Do I suffer from repeated implantation failure?
You have a problem with the implantation of your embryos when there is no positive pregnancy test:
- after at least two treatment cycles with transfer of either fresh or thawed embryos,
- with (in all) at least four transferred embryos in a good cleavage stage (4, 6 or 8 cells)1 or at least two blastocysts2,
- with good quality embryos.
Causes can be:
- attempted pregnancy at advanced age,
- (in the lab) good embryo development up until cleavage stage but failure at blastocyst level,
- difficult embryo transfer,
- difficult embryo hatching,
- anatomical problems with the uterus, ovaries or fallopian tubes,
- endometrial receptivity problem,
- systemic maternal factors,
- genetic factors of (one of) the prospective parents.
However, in many cases we cannot explain the reason for repeated implantation failure.
Your doctor might propose the following actions:
- monitoring of embryo transfer via vaginal ultrasound to optimise implantation in the uterus;
3 Hatching is the embryo ‘coming out of its skin’ so that it can attach itself to the lining of the womb. Normally speaking the zona pellucida around the embryo is weakened and dissolved by digestive enzymes produced by the lining of the womb after ovulation. Sometimes this does not happen (efficiently) or the skin is too hard, which means it does not dissolve. In assisted hatching we help the embryo to attach by making a hole in the skin with a special laser.
4 Dating of the endometrium means we check whether it is ready for embryo implantation. This is only the case during a number of 24 hours periods in the menstrual cycle (the so-called ‘window of implantation’). If the embryo is transferred to the uterus outside this period, it cannot implant.
application of ‘assisted hatching’3, whereby the protective skin around the embryo (the zona pellucida) is worked on with a special laser to facilitate implantation of the embryo in the endometrium,
- blastocyst culture can be performed to see whether your embryos have the capacities and qualities to survive until day 5 of embryonic development;
- performance of a hysteroscopy to rule out anatomical problems at uterine level.
- performance of a laparoscopy to rule out endometriosis (migration of lining of the womb outside the uterus) or hydrosalpinx (= swollen tube). If one of these is detected, treatment can follow accordingly. For instance, endometriosis can be treated via a therapeutic laparoscopy.
- monitoring the receptivity of the lining of the womb (endometrium):
- we can find out whether there is an infection and if so, treat it;
- histological dating can be performed4 and our treatment can be adjusted based on this. We take a bit of endometrium tissue (see endometrium biopsy) and examine it in the lab;
- we can also perform a genetic analysis to detect the best time of receptivity of your endometrium and thus for embryo transfer. This is referred to as ERA Testing (Endometrial Receptivity Analysis). This is performed in co-operation with Igenomix in Spain. For more information: www.igenomix.com/tests/endometrial-receptivity-test-era;
- endometrial scratching can be performed (with a fine catheter) in an attempt to augment endometrial receptivity;
- transfer of (a) thawed embryo(s). An IVF/ICSI cycle in which all your embryos are frozen and thawed afterwards can be considered to improve endometrial receptivity (by using your natural cycle for transfer (FrET or Frozen Embryo Transfer)) ;
- a thorough medical evaluation of the (prospective) mother. Systemic problems can be diagnosed and treated where needed:
- if it concerns a genetic abnormality, PGD can be offered, i.e. the genetic diagnosis of the embryos before one is transferred (see the separate website of the PGD-clinic);
- in cases of extreme implantation failure, if the (prospective) parents have normal genes and your embryos are good morphological quality, PGS can be offered. This is preimplantation screening of the embryos in the blastocyst phase. This screening checks whether the chromosomal organisation is normal;
- empirical associations of medications – such as heparines or aspirins (to stop clotting) and (short-term use of) corticosteroid are avoided as much as possible in our clinic due to the lack of evidence. In specific situations they can be discussed.
As a last resort and only in extreme cases, despite a good embryo morphology, oocyte donation can be an option to help RIF patients conceive.
Decisions should always be made in joint consultation with your doctor who is fully aware and up to date with your specific case.
This data is treated strictly confidentially and anonymously. We aim to find the reasons (unknown to date) that may explain your condition with the aim of finding out why you have this problem. At the same time we try to improve our approach of the problem.
Our long-term goal is to develop drugs that may help prevent or treat implantation failure. Although this process might take years to reach the development of treatment, it might help others with this problem in the future.