Implantation

• Inner cell mass and trophoblastic region are defined during embryonic development.
• Oogenesis occurs during the first half of the menstrual cycle, while implantation occurs during the second half.
• Implantation occurs about seven days after fertilization, when the zona pellucida degenerates and the blastocyst attaches to the endometrial epithelium through trophoblast adjacent to the embryonic pole.
• Changes must occur in both the blastocyst and the uterine epithelium to allow blastocyst attachment and the initiation of implantation.
• The uterus cycles through receptive and non-receptive stages.
• Entry into the receptive stage, during which implantation is possible, is controlled by estrogen and progesterone.
• The receptive endometrium is covered by pinopodes of endometrial cells and contains cell adhesion molecules (Integrin), hormones, cytokines, and growth factors.
• Some of these latter factors, such as metalloproteases, play a role in trophoblastic invasion of the endometrium, in addition to functioning in attachment.
• Both trophectoderm cells and pinopodes contain trophinin, allowing cell adhesion by trophinin-trophinin binding.
• Blastocysts mature to the attachment-competent stage and express perlecan, a heparan sulfate proteoglycan, on their surface.
• Heparan sulfate proteoglycans are known to have a high degree of specific binding to various extracellular matrix proteins and growth factors/cytokines and thus could serve as attachment factors.
• In addition to heparan sulfate proteoglycans, other factors possibly involved in adhesion include selectins, integrins, metalloproteases, and trophinin-tastin-bystin.
• Trophoblast cells stimulated by trophinin-mediated cell adhesion invade maternal cells.
• Implantation involves synchronization between the invading blastocyst and a receptive endometrium.
• Endometrial cells lose glycocalyx and develop pinopodes.
• Estrogen, acting through the estrogen receptor, stimulates the uterine endometrium to undergo proliferation by inducing the production of growth factors such as insulin-like growth factor 1.
• Estrogen also prevents programmed cell death within the uterine epithelium.
• Progesterone, acting through the progesterone receptor, induces the transcription factor hand2, which allows implantation to occur.
• As the uterus enters the receptive stage, its apical glycocalyx decreases in amount and apical microvilli, which are normally abundant, retract to establish a flattened surface in many areas of the epithelium, and large apical protrusions called pinopodes form.
• The blastocyst undergoes maturation from an attachment-incompetent stage to an attachment-competent stage.
• Each fetus in dizygotic twins has its own amnion and chorion.
• Multiple pregnancies can result in dizygotic twins, monozygotic twins, or higher order multiples such as triplets, quadruplets, quintuplets, or sextuplets.
• Twins occurs when more than one fetus simultaneously develop in the uterus.
• There can be two placenta in dizygotic twins, either completely separated or fused at the margin.
• Genetic features also differ in dizygotic twins.
• The sex of the fetus may be different in dizygotic twins.
• If the division takes place within 72 hours after fertilization (prior to morula stage), embryos will have two separate placenta, chorion, amnions.
• If the division takes place between 4th and 8th day after the formation of inner cell mass when chorion has already developed, it is diamniotic monochorionic twins.
• Superfecundation, the fertilization of two or more oocytes at different times, can occur in dizygotic twins.
• Monozygotic twins can occur at different periods after fertilization.
• Risk factors of twin pregnancy include increasing maternal age, high parity, IVF infertility therapy, and genetic race.
• Monozygotic twins originate from one zygote and are genetically identical, of the same sex, and similar in physical appearance.
• If the division takes place after 8th day after the formation of inner cell mass when amniotic cavity has already formed, it is monoamniotic monochorionic twins.
• Dizygotic twins can result from fertilization of two ova, ovulated from two Graafian follicles, by two sperms.
• Monozygotic twins can result from division of embryoblast, early separation of embryonic blastomeres, or division of embryonic disc.
• Dizygotic twins originate from two zygotes and are increased with maternal age and hereditary tendency.
• Ovarian mole is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and will fail to come to term.
• Blastocyst sinks beneath the endometrial epithelium and the defect is filled by a closing plug.
• Decidual cells degenerate adjacent to the penetrating syncytiotrophoblast, and the syncytiotrophoblast engulfs these degenerating cells, providing a rich source of nutrition for the embryo.
• Human embryo is completely embedded in the endometrium by Day 10 and completely regenerated uterine epithelium covers the closing plug by Day 12-13.