Implantation
Time period:
days 5–13
At this
early stage of development timings are very individual and often a range is
more appropriate. All timings described here are the typical ages documented in
a range of literature.
Implantation
The
travelling morula enters the uterus at approximately day 4 and begins to form a
blastocyst at around 4.5 days. It begins the process of implantation roughly a
day later (6–7 days). Implantation occurs to enable the developing embryo to
take oxygen and nutrients from the mother, thus enabling its growth.
For the
blastocyst to implant successfully the walls of the uterus make certain
preparations. The endometrial lining of the uterus undergoes changes every
month as part of the menstrual cycle. There are three main stages: the proliferative
(or follicular) phase, the secretory (luteal or progestational) phase and
the menstrual phase.
The proliferative
phase begins on day 5 of an average menstrual cycle and finishes on day 13,
prior to ovulation. Changes to the uterus during this phase include an increase
in thickness of the endometrium and an increase in vascularisation.
During the secretory
phase arteries and glands become coiled and secretions increase helping to
maintain the thickness of the endometrium. There are three distinct layers of
the endometrium: a superficial compact layer, a middle spongy layer
and a deep basal layer.
There is
also a group of new rounded cells that cover the whole surface of the
endometrium. These are the decidual cells. If fertili sation does not
occur the spongy and compact layers and the decidual cells are shed.
Decidualization
is the collective term for the changes that the endometrium undergoes in
pregnancy. Decidual cells have a high secretory capacity of laminin and
fibronectin (both have adhesive qualities) and the vascularity of the tissue is
improved. At implan tation these cells accumulate fats and glycogen.
The decidua
remains important and has a role in the develop ment of the placenta (see
Chapter 13).
The phases
of the menstrual cycle are coordinated by hormones (Figure 12.1).
Follicle stimulating hormone (FSH), secreted from the
anterior lobe of the pituitary gland, initiates the maturation of a few
follicles in the ovary. A day before ovulation the pituitary gland also
releases a surge of luteinising hormone (LH) inducing the ovary to
release an ovum.
The empty Graafian
follicle (see Chapter 9) matures and produces oestrogen. In a positive
feedback loop the oestrogen induces more FSH and LH to be produced by the
pituitary and consequently more oestrogen is produced. This causes the
thickening of the endometrium.
The Graafian
follicle matures into the corpus luteum and begins to produce
progesterone as well as oestrogen. Progesterone maintains the developing
endometrium and increases the uterine gland secretions. The presence of
progesterone and oestrogen inhibits production of FSH and LH dropping the
levels of both hormones.
Upon
fertilisation and implantation the trophoblast cells produce human chorionic
gonadotrophin hormone (hCG) causing the corpus luteum to continue
progesterone production.
The location
for implantation is commonly superiorly on the anterior or posterior walls of
the uterus (Figure 12.2).
At
implantation the blastocyst comprises a fluid‐filled core, an outer cell mass
(trophoblast) and an inner cell mass (embryoblast) at the embryonic pole
(Figure 12.3).
The process
of implantation can be broken down into four stages. The first is hatching,
as the developing blastocyst has to ‘hatch’ out of its surrounding zona
pellucida. Apposition follows, as the tropho blast cells come into
contact with the decidua of the endometrium. If the embryonic pole is not
closest to the area of contact the inner cell mass rotates to become aligned
with the decidua. Then adhesion occurs and molecular communication
between blastocyst and endometrial cells is vastly increased. Finally, invasion
of the endometrium by the trophoblast begins.
By day 8
implantation has begun and the blastocyst develops again into a more complex
structure. The inner cell mass differentiates into an epiblast layer and
a hypoblast layer (Figure 12.4). The hypoblast layer is located nearer
to the blastocyst cavity. These two layers are now called the bilaminar disc.
Simultaneously
another cavity forms within the epiblast, called the amniotic cavity.
The cells of the hypoblast will develop into the extraembryonic membranes
(amnion, yolk sac, chorion and allantois) and the epiblast will develop to form
the embryo (Figure 12.5).
Clinical relevance
Implantation
can be negatively influenced by many factors at any stage of the process. This
is a common cause of miscarriage, especially for couples undergoing IVF
treatment.
Immunosuppressant
cytokines are produced during implantation to prevent an immune reaction, and
some autoimmune diseases (systemic lupus erythematosus and
antiphospholipid syndrome) can mean the mother’s body attacks the embryo at
implantation.
If
implantation occurs near to the internal os of the cervix the placenta can
develop in a dangerous position (placenta praevia) which can result in
severe bleeding in later pregnancy and labour.
Intrauterine
devices (IUDs) used for contraception were originally intended to prevent
implantation of the blastocyst by irritating the endometrium. It is likely that
instead they work by inhibiting sperm and ovum migration and fertilisation.
Medicated IUDs also contain progester hibits FSH and LH release, preventing
ovulation.
