Embryo Implantation: Process and Common Symptoms

By (embryologist) and (babygest staff).
Last Update: 09/25/2019

The implantation of a fertilized egg, already called an embryo, is the process that occurs when the embryo attaches to the endometrium (the inner layer of the uterus). In an IVF cycle, embryo implantation occurs after transfer and marks the beginning of intrauterine embryonic development and the first symptoms of pregnancy.

What is implantation of the fertilized egg?

Embryo implantation is the moment when the fertilized egg is detached from its sheath (zona pellucida), adhered to the endometrium and anchored to it to begin its intrauterine development.

The embryo that performs the implantation is in blastocyst stage, which is reached between 5 and 6 days after fertilization. At this stage of embryonic development, the blastocyst has approximately 200-400 cells, differentiated into two different cell types:

Trofoectoderm or trophoblast
are the cells of the outermost part and are the ones that will give rise to the placenta and other types of embryonic structures.
Internal cellular mass (ICM)
these cells are what will give rise to the embryo itself.

In addition to these two distinct cell types, a central cavity is formed known as a blastocele. In this image we can see the structure of the blastocyst, i.e. the embryo prepared for uterine implantation.

For implantation to take place and pregnancy to be achieved, there are two key factors:

Embryo quality
the fertility clinic evaluates and classifies embryos on the basis of their quality. The one or those (if two embryos are transferred) with the best prognosis and the greatest implant potential will be selected for the transfer.
Endometrium preparation
in order for the embryo(s) to implant, the endometrium must be receptive, i.e. have the appropriate appearance and thickness for embryo nesting. For this, the woman must take hormonal medication (estrogens and progesterone). These endometrial changes are what we know as decidualization.

These aspects allow for adequate synchrony and interaction between uterus and embryo. Therefore, if good quality embryos are transferred to the woman with a suitable endometrial preparation, the likelihood of achieving pregnancy increases.

Embryo implantation step by step

The period of implantation of the embryos in the female uterus consists of several phases: detachment of the zona pellucida, pre-contact and apposition, adhesion and invasion. In the following image we can see the stages of implementation, although we explain them in detail below.

Detachment of the zona pellucida

The first step for the embryo to implant is to leave its shell: the zona pellucida. It's what's known as hatching. It consists of the breakage of the zona pellucida and the exit of the embryo, both from the ICM and from the trofoectoderm.

Pre-contact and apposition

Approximately between day 5 and 6 of embryonic development, the fertilized egg is positioned in the endometrial tissue and remains immobile in the acquired position. It only directs the embryonic pole (where the ICM is) towards the epithelium of the endometrium.

In this phase, the so-called pinopods, projections of the endometrial cells that help the blastocyst at the junction with the endometrial epithelium, are fundamental.

Pinopods only appear during the implantation window (explained below) and disappear approximately on the 24th day of the cycle.

Adhesion

This is the moment when the trofoectoderm cells strongly bind to endometrial cells through adhesion molecules such as integrins, L-selectins, proteoglycans, fibronectins, etc.

Invasion

This usually occurs from day 8-9 of embryonic development.

Little by little, the cells of the trofoectoderm proliferate towards the endometrium and thus manage to displace and replace the endometrial cells. This eventually leads to complete invasion of the endometrial stroma by the trophoblast, which becomes totally embedded in the endometrium.

When does the implantation take place?

Implantation lasts approximately 4-5 days, from the time the embryo leaves the zona pellucida (hatching) until the trofoectoderm completely invades the endometrium to initiate the formation of the placenta and allow embryonic development to continue.

Generally, implantation begins when the embryo is 6 days old, that is, about 6 days after fertilization. For the blastocyst-stage embryo to adhere to the endometrium, it is essential that there is adequate communication between the two, which is only possible during the so-called implantation windowwhich spans more or less from day 20 of the female cycle through 24-25.

The implantation window is no more than the period in which the uterus has the necessary qualities to allow the implantation of the embryo. It's what we know as the receptive uterus.

The main qualities of the receptive endometrium are:

Trilaminar aspect
in the ultrasound we can see three parallel lines.
Thickness
should be between 6 and 10 mm approximately.

The passage from the nonreceptive to the receptive uterus occurs only under the hormonal influence. For this reason, it is essential that the woman to whom the embryo or embryos are to be transferred receives estrogen and progesterone supplements to allow the endometrium to move from its nonreceptive state to its deciduous or receptive state.

In cases of surrogacy it is the surrogate pregnant woman who will receive hormonal treatment that will allow her endometrium to become receptive and, thus, the embryos transferred can implant.

Symptoms of implantation

The implantation of the fertilized egg does not always give rise to specific symptoms by which we can confirm that the embryos have implanted in the uterus.

However, there are women who experience certain symptoms or signs on the days of nesting that may make us suspect that implantation has occurred. Some of the most common are:

  • Implantation bleeding (light, light-colored, low-intensity bleeding)
  • Abdominal pain
  • Breast swelling
  • Increased urge to urinate
  • Gastrointestinal disorders (diarrhea or constipation)
  • Nausea and/or vomiting
  • Cramps
  • Abhorrence of certain odors and/or foods

These symptoms are a consequence of the hormonal change characteristic of pregnancy, especially strong in the first few weeks after implantation. Therefore, we can say that, with the exception of implantation bleeding and cramps, they are not symptoms of nesting per se, but of early embryonic development (post-implantation).

In the following article you can read more information about this process: Symptoms after embryo implantation.

FAQs from users

Does embryo implantation in surrogate mothers differ from embryo implantation in normal IVF cycles?

By Andrea Rodrigo (embryologist).

Embryo implantation in the surrogate mother is exactly the same procedure as in normal IVF cycles. The embryo does not understand if it is in the uterus of the future mother or in the uterus of the surrogate mother. All it needs is for the uterus in which it has been transferred to be receptive, that is, to have the optimum qualities so that it can be implanted in it and continue its development.

Are the symptoms of embryo implantation in IVF more severe or noticeable than in a natural pregnancy?

By Andrea Rodrigo (embryologist).

Medication administered during fertilization treatment in vitro (IVF) may increase the intensity of symptoms after implantation. Also, the psychological factor plays an important role in this sense, as emotional involvement in IVF treatments can aggravate the symptoms or their sensation.

How does implantation in frozen embryos occur?

By Andrea Rodrigo (embryologist).

When we talk about embryo transfer and embryo transfer of frozen embryos we don't refer to the transfer of frozen embryos but to the process of embryo transfer after being frozen and thawn. So, once in the uterus, implantation happens exactly the same way, regardless of whether the embryos have been created in the same cycle or if they come from previous cycles and, therefore, have bean frozen for a certain period of time.

Can several embryos be implanted at the same time?

By Andrea Rodrigo (embryologist).

Of course. This is what would result in multiple pregnancy. For example, the implantation of two embryos results in a twin pregnancy, the implantation of three in the gestation of triplets, etc.

In cases of IVF, be it own IVF or IVF in surrogacy, the embryo transfer with the highest amount of embryos facilitates multiple pregnancy.

Suggested for you

We have commented that it is necessary for the woman to whom the embryos are transferred to receive a hormonal treatment of endometrial preparation to favour the implantation of the embryos. Do you want to know what this treatment consists of? In this link you’ll get more information: Endometrium preparation

In addition to the proper condition of the endometrium, we have also mentioned that it is essential that the transferred blastocyst be of quality. If you want to know more about embryo quality, I recommend you consult this link: How is the quality of embryos measured?

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References

Authors and contributors

 Andrea Rodrigo
Andrea Rodrigo
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia. Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia along with the Valencian Infertility Institute (IVI). Postgraduate course in Medical Genetics. More information about Andrea Rodrigo
Adapted into english by:
 Romina Packan
Romina Packan
Babygest Staff
Editor and translator for the Babygest magazine in English and German. More information about Romina Packan

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