Embryo Implantation Failure: Causes, Symptoms & Treatments

By (embryologist) and (babygest staff).
Last Update: 11/29/2017

Implantation failure refers to the inability to achieve pregnancy because the embryo, once fertilized by the union of egg and sperm, fails to adhere to the uterine wall to form the gestational sac.

It is difficult to find out if the cause of infertility in a couple is due to implantation failures, as it is not possible to know whether or not fertilization takes place during the search for a natural pregnancy.

On the other hand, it is more common to speak of implantation failure in an in vitro fertilization (IVF) treatment when, after several embryo transfers, the result is always negative.

What is embryo implantation?

The embryo implantation in the uterus consists of the adhesion of the embryo to the endometrium, the inner layer that covers the uterus. Once implanted, the embryo continues its development, the gestational sac and placenta are formed, and gestation begins for the next 9 months.

For the phenomenon of implantation to take place, the endometrium must be receptive. This means that the endometrium must have the thickness and qualities necessary to receive the embryo. In addition, implantation occurs when the embryo is about 6-7 days old and in the stage known as blastocyst.

The period of time when there is a perfect synchrony between the blastocyst and the endometrium is the implantation window, which can last several days.

Implantation failure

Implantation failure is the loss of a viable embryo because it is not able to synchronize with and attach to the endometrium.

Usually, we speak of implantation failure in women or couples undergoing assisted reproduction treatment when, after having kept an embryo in culture for its development and having transferred it to the maternal uterus, IVF does not work.

Specifically, implantation failure is considered to exist when the woman has not achieved pregnancy after 3 complete IVF cycles, with the transfer of about 6 or more embryos, or after 2 egg donation cycles.

Also, the following requirements must be met during IVF in order for the infertility problem to be considered implantation failure:

  • Good quality embryos are transferred.
  • No problems arise during embryo transfer, such as the inability to introduce the cannula through the cervix.
  • There are no problems in the uterus.

These implantation failures provoke a great frustration in the future parents who, without knowing why, do not get pregnant.

Causes

It is very difficult to find out why embryo implantation does not occur after several attempts. However, we can divide the most normal causes of this implantation failure as follows:

Embryonic Causes
genetic alterations in the embryo or in the gametes of the progenitors (egg and sperm), alterations in the zona pellucida of the embryo which prevent hatching, etc.
Uterine Causes
infections, endometrial polyps, fibroids, endometriosis adhesions, uterine malformations, hydrosalpinx, etc. A displacement of the implantation window may also occur, which does not correspond to embryonic development.
Systemic Causes
thrombophilias, endocrine alterations (diabetes, hyper- or hypothyroidism), autoimmune diseases (antiphospholipid syndrome), etc.

Despite this, the cause of repeated implantation failures is unknown in 40% of cases. One possible explanation is that there are problems in the communication between the endometrium and the embryo, which fails to complete the implantation process.

Diagnosis and treatment

Although the diagnosis of implantation failure is difficult, a series of tests must be carried out before effective treatment can be applied to increase the likelihood of pregnancy.

The result of these diagnostic tests will help specialists personalize fertility treatment as much as possible. Next, we will comment on some diagnostic tests of the implantation failure:

  • Parent karyotype
  • Hysteroscopy or hysterosalpingography to view the uterine cavity
  • Endometrial biopsy to study endometrial receptivity
  • Studies of thyroid clotting or function
  • Immunomodulation test for immune rejection of the embryo

Depending on the results of these tests and the most probable cause of the failure to implant the embryos in the uterus, the appropriate treatment will be outlined.

Preimplantation Genetic Diagnosis (PGD)

When a woman presents an advanced maternal age and/or low ovarian reserve, it is very probable that the fertilized embryos present chromosomal alterations, although apparently their morphological quality is good.

To avoid transferring these altered embryos after IVF treatment, assisted reproduction laboratories use the technique of preimplantation genetic diagnosis or PGD. This consists of a genetic analysis of the embryos with the aim of selecting only chromosomally healthy embryos.

PGD is also the most appropriate technique when the karyotype of the parents has been altered.

Extended culture to blastocyst

Extended culture consists of keeping the embryos in in vitro culture for 5 days, until they reach the blastocyst stage. Embryo transfer, therefore, is done on day 5 instead of day 3.

With the extended culture it is possible to make a natural selection of the embryos with greater implantation capacity, since the embryos of lower quality do not manage to develop to blastocysts and stop their development earlier.

Surgical techniques

Surgical interventions to solve repeated implantation failures are only effective when there are alterations in the structure of the uterus or in the fallopian tubes.

For example, IVF patients with hydrosalpinx tend to have lower success rates. Therefore, by performing a bilateral salpinguectomy to remove fluid from the tubes, the chances of achieving pregnancy are increased.

On the other hand, laparoscopy or hysteroscopy are the appropriate techniques when there are septa, polyps or fibroids that deform the uterine cavity and prevent the correct implantation of the embryo.

Finally, it is worth mentioning endometrial scratching as a novel technique to renew the endometrium and increase its receptivity.

Endometrial Receptivity Analysis (ERA)

The Endometrial Receptivity Array (ERA) is a diagnostic test that provides information about endometrial receptivity at a given point in the menstrual cycle.

To do this, it is necessary to do an endometrial biopsy and check which is the best day to do the embryo transfer, that is, when the endometrium is more receptive.

This technique is very useful to find out if there is abnormalities in the implantation window. If it is confirmed that this is the cause of implantation failure, the appropriate procedure would be to vitrify the embryos and transfer them at the moment of maximum endometrial receptivity.

Pharmacological treatment

Some drugs may favour embryo implantation if endocrine alterations, thrombophilic factors or immune alterations are shown to exist.

For example, aspirin and heparin are very effective drugs for reducing blood clotting in women at risk of thrombophilia. In this case, the treatment should last throughout the pregnancy until the baby is born.

On the other hand, in the case of infections of the female reproductive system, it is advisable to carry out a treatment with antibiotics so that the uterus is not inflamed and the endometrial receptivity is adequate.

Egg and Embryo Donation

If all diagnostic studies of uterine or endometrial problems are normal and the cause is most likely embryonic, gametes donation should be considered to avoid implantation failure.

In most cases, and especially when the woman is elderly, egg donation is a treatment that offers very good results. Eggs from healthy, young donors have high implantation rates.

When there is a severe male factor that may influence implantation, donor sperm may also be the most appropriate option for couples with repeated IVF failures.

Surrogacy

In those occasions where repeated implantation failures are inexplicable and pregnancy has not been achieved despite having done the most indicated treatments, the last possible option is to resort to surrogacy.

Surrogacy is an assisted reproduction technique in which fertilized IVF embryos are transferred to a healthy woman, called a surrogate, to take charge of gestation of the baby throughout the pregnancy.

The embryos transferred to the surrogate can be those of the couple if they are of good quality, with which they would have a biological child, or fertilized from the gametes of donors.

FAQs from users

What could be the cause of an implantation failure in the egg donation receptor?

By Zaira Salvador (embryologist).

In egg donation, the embryos obtained are of very good quality and it is assumed that they have no genetic alterations. Therefore, if there are implantation failures after 2 egg donation cycles, the most probable causes will be related to uterine problems in the recipient woman.

What are the symptoms of implantation failure?

By Zaira Salvador (embryologist).

After an embryo transfer, there is no sign or symptom that can tell us for sure if IVF has worked or not. In general, if the embryo has not implanted, about 15 days later the premenstrual symptoms will begin and, finally, menstrual bleeding will arrive to confirm the implantation failure.

Can there be miscarriage due to implantation failure?

By Zaira Salvador (embryologist).

When there is an implantation failure, the embryo has not yet attached to the uterus nor has the gestational sac formed. Therefore, there is no abortion per se. The transferred embryo that has not been implanted stops its development and is eliminated with the woman’s next menstruation.

Suggested for you

Implantation failures can occur both in the search for a natural pregnancy and in IVF treatments. However, it is more common to speak of implantation failure after repeated IVF failures. To find out more about this treatment in detail, you can read on in the following post: What Is IVF Surrogacy? – Process, Success Rates & Cost

If you are interested in surrogacy due to repeated implantation failures, we recommend you consult all the information in the following article: What Is Surrogacy & How Does It Work? – Everything You Should Know

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References

Authors and contributors

 Zaira Salvador
Zaira Salvador
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia (UPV). Embryologist specializing in Assisted Procreation, with a Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI). More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Marie Tusseau
Marie Tusseau
Babygest Staff
Editorial Director of Babygest magazine in French and English. More information about Marie Tusseau

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