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.
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).
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.