By Zaira Salvador BSc, MSc (embryologist).
Last Update: 02/14/2018

Implantation failure refers to a situation in which a woman wishes to become pregnant but she is unable to fulfill her dream despite having unprotected sexual intercourse on a regular basis.

The main problems these couples face is that they actually don’t know if theirs is a case of Repeated Implantation Failure (RIF), or if their gametes are actually unable to meet each other and subsequently fertilization never occurs.

A diagnosis of RIF can only be confirmed after several failed IVF attempts, which is to say, if an embryo has been cultured and placed into the uterus of the mother-to-be but has not lead to an ongoing pregnancy.

What is embryo implantation?

Implantation is the process whereby the embryo attaches to the uterine lining during the implantation window of the woman. It takes place within 6-7 days after fertilization, thereby giving raise to a new pregnancy.

The implantation window of females is a period of 2 to 6 days during which the the uterus is receptive for implantation, which is to say, it has the optimum conditions to receive the embryos and allow them to attach.

The embryo implantation process can be split into two phases:

Pre-implantation stage
It encompasses the preparation of the endometrial lining, early embryonic cleavage, and apposition.
Implantation stage
Once at blastocyst stage, the embryo attaches to the uterine lining.

As one shall see, embryo implantation is a challenging process that requires a healthy embryo and a receptive uterus in order for synchronization between them to occur effectively.

Implantation failure signs

We can begin to suspect implantation failure has taken place when a patient hasn’t achieved an ongoing pregnancy after 3 IVF cycles using own eggs, or after 2 donor-egg cycles, as long as:

In these cases, we recommend that patients consider undergoing other treatment options in order to increase the implantation rates.

What causes implantation problems?

There exist several causes that may lead to embryo implantation failure, either related to the embryo, the uterine lining of the patient, or specific diseases.

Embryonic causes

They are fundamentally due to genetic alterations in the embryo or the reproductive cells of the parents (the egg and/or sperm).

Also, some embryos present abnormalities in the zona pellucida (ZP), which prevent them from breaking out of the ZP and detaching from it.

The zona pellucida (ZP) is a glycoprotein sphere that surrounds the egg cell. It can be found around the embryo following fertilization as well.

Reduced endometrial receptivity

Certain factors affect the receptivity of the endometrium, including:

  • Chronic endometritis (CE)
  • Alterations of the uterine cavity, such as polyps, uterine septae or intrauterine adhesions
  • Abnormalities in the implantation window. For example, when it occurs before or after 6-7 days post fertilization.

Some of these abnormalities can be treated with medications or with determined techniques such as hysteroscopy.

Systemic causes

Oftentimes, the problems are due to abnormalities that have nothing to do with the female reproductive system, such as:

Thrombophilia
blood clotting disorders.
Immunological disorders
the embryo is rejected by the mother’s immune system, which recognizes it as a “foreign invader”.

Unfortunately, the reasons why these causes compromise the embryo implantation process are still unknown. New diagnostic tests that allow a better management of these complications are being investigated nowadays.

Management & treatment

The different ways to manage RIF and the possible options for its treatment are listed below:

Culture to blastocyst

Sequential culture can be used with the embryos of patients who experience RIF in order to examine their development to blastocyst. For this reason, the embryo transfer will be done on day 5. At this point, the embryologist is able to detect the presence of potential anomalies in the embryo should they be present.

Learn more: What Is Blastocyst Culture & Transfer?

Preimplantation Genetic Diagnosis (PGD)

The chances for implantation failure increase with advanced maternal age due to the presence of an increased number of chromosomal abnormalities in the egg cell. Preimplantation Genetic Diagnosis (PGD) allows us to select only healthy embryos for the transfer. PGD is a technique whereby a cell is removed from the embryo (i.e. biopsy), a process that doesn’t affect its development at all.

See this for more: What Is PGD or Preimplantation Genetic Diagnosis?

Heparin administration

Some women with risk of thrombophilia are prescribed aspirin and heparin, an option that is usually very effective to deal with RIF.

Heparin is a natural anticoagulant (blood thinner) that can be found in various tissues of the human body.

Endometrial Receptivity Analysis (ERA)

The Endometrial Receptivity Analysis (ERA), also called Endometrial Receptivity Array, is a molecular diagnostic tool that allows us to examine the expression of a set of genes that are closely linked to the endometrium. In other words, ERA provides us with information about endometrial receptivity with just a biopsy.

Moreover, ERA is able to detect abnormalities in the implantation window, if any. Should this be the cause, patients are recommended to opt for embryo vitrification. IVF embryo transfer can be postponed up until the moment when their endometrium is more receptive.

Assisted Hatching

With assisted hatching, the embryologist creates a small hole in the zona pellucida of the embryo through which the embryonic cells can hatch out.

This technique is highly effective because it allows the embryos with a thick zona pellucida to be able to implant. To give you an idea, ehen thickening is present in embryos, they resemble a flattened olive.

Egg donation

Egg donation may be the best solution in cases of repeated implantation failure when the uterus and the endometrial lining are normal. Implantation rates are excellent in patients who use donor eggs, given that embryo quality is significantly higher.

Surrogacy

When implantation failure is due to unexplained causes and none of the treatments listed above is effective, surrogacy may be an option to build your family. The main advantage is that it allows the intended mother to use her own eggs, as long as good quality embryos were obtained in previous IVF cycles.

More on this story: What Is Surrogacy & How Does It Work? – Everything You Should Know.

How to calculate the costs

The possible infertility treatment options to deal with recurrent implantation failure are expensive, especially if pregnancy is not achieved the first time.

In the case of IVF, the average cost of single cycle IVF packages ranges between $8,500 and $12,000. More often than not, this price range doesn’t include the cost of fertility drugs, which add a considerable amount to this sum. PGD or ERA, if needed, are additional techniques that shoot up the price of IVF.

In case none of these options works and you decide to move on to donor eggs, a complete egg donation cycle typically costs $26,000 on average, which includes the donor’s fee ($7,000 approximately) plus $400 for short-term medical insurance for the egg donor.

As regards surrogacy, it can cost up to $90,000-$130,000 or more, depending on the US state where it takes place and the particular circumstances of each case.

Assisted procreation, as any other medical treatment, requires that you rely on the professionalism of the doctors and staff of the clinic you choose. Obviously, each clinic is different. Get now your Fertility Report, which will select several clinics for you out of the pool of clinics that meet our strict quality criteria. Moreover, it will offer you a comparison between the fees and conditions each clinic offers in order for you to make a well informed choice.

FAQs from users

Do low progesterone levels cause implantation failure?

By Zaira Salvador BSc, MSc (embryologist).

Yes. Progesterone has a key role in maturing the uterine lining for embryo implantation. Low levels of progesterone after ovulation (i.e. luteal phase deficiency) might lead to implantation failure.

Why does implantation failure occur with donor eggs?

By Zaira Salvador BSc, MSc (embryologist).

In spite of having high-quality embryos with a normal development rate, unfortunately some egg donor cycles fail when the uterus is not receptive. Implantation will never take place in a non-receptive uterus.

Suggested for you

We have explained that implantation failure occurs after embryo transfer in IVF cycles. To learn more about this technique step by step, click here: What Is In Vitro Fertilization (IVF)? – Process, Cost & Success Rates.

To gain a much deeper insight on the process of implantation, we recommend that you visit the following post: What Is Embryo Implantation?

What are the earliest signs of embryo implantation? Get more info by clicking the following link: What Are the First Signs & Symptoms of Embryo Implantation?

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Authors and contributors

 Zaira Salvador
BSc, MSc
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
License: 3185-CV
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