so in this second part of still the early embryonic series we are going to talk about the process of implantation but we'll also look at the disorders of implantation remember when the first week ends implantation that the concept as is ready for implantation just a review of what i've just of what we learned in the first week of development is that the concept has been propelled from the site of fertilization toward the site of implantation during that movement there are some morphological changes that the concept has undergone we say that become the zygote first then two cell stage then for cell stage then modula and then blastocyst at the end of the first week we have a structure which you call the blastocyst and the blastocyst has two cell populations the inner cell mass embryoblast and the outer cell mass trophoblast these are the parts of the blastocyst that's the inner cell mass which is the embryoblastic tissue this is the outer cell mass which is the trophoblastic tissue we also learned that this is the blastocyst cavity this is the embryonic pole which is used to lead the way during the hatching process and this is the embryonic pole [Music] which is now going to lead the way during implantation so when the first week ends we are ushered into the second week what happens in the second week during the second week of development the blastocyst will implant and so we will now establish the pregnancy remember initially the woman had conceived but we cannot say that she was pregnant but when implantation takes place then the pregnancy is established that will be the subject matter of this class however the other things that also take place during the second week there's some morphological changes that take place involving the inner selmas as well as the outer cells we will not look at them in this lecture look at them in the next lecture during the second week we also have establishment of fetal membranes again we'll not look at them in this lecture and generally the second week of development is known as the week of twos again the concept of the tools will not look at them here i've just put these concepts here so that you understand that even as implantation is taking place many other things are also taking place but because we are splitting this lecture we're not having those ones here in this lecture we're just going to focus on implantation so this is the objective of this lecture one is to define what is implantation and state its normal site then we are going to look at the key steps that take place during the process of implantation we will highlight some critical hormonal changes which take place during the process of implantation and lastly we'll explain some conditions which are due to abnormal implantation process so let's start with the first one let's define implantation and state its normal science by definition implantation is the process by which the blastocyst attaches itself and also embed itself into the endometrial lining of the uterine wall well i am underlying in the metal lining because that's a normal site sometimes you may have it implanting on other sides other than that and we are going to talk about that shortly the common sight in the uterus where the blastocyst will attach itself at the upper parts of the train segment what we call the fundus of the uterus the process of invasion and embedding that occurs during implantation is done by the outer selmas of the conceptus it is the trophoblast that invades the maternal tissues now that we've talked about its implantation taking place in the furnace perhaps a good time to just tell ourselves about the part of the so that we are familiar with what you're talking about so this is the uterus this is the fundus of the uterus which correspond with that is the body of the uterus which corresponds with around there and this is the cervix which correspond with that part the junction between the cervix and the body is called the is mass of the uterus confuse the isthmus of the fallopian tube and this point where the fallopian tube attaches called the corners of the uterus so we are saying that the concept has attaches on the funding side so we'll expect it to be attaching somewhere here if it attaches there then we call that one fandom anterior and if it attaches there we call that fungal posterior it can either touch phantom anteriorly or funder posteriorly in terms of the cross-sectional anatomy histological layers of the uterine wall remember uterus has three layers the outermost layer is called the perimetrium the middle layer is called the myometrium and the innermost layer is known as the endometrium the myometrium is the muscular layer that muscular layer contain large blood vessels as you can see here that layer of blood vessels within the myometrium is called the stratum vascularis so in this image we see the blood vessels running within the myometrium there that will be the stratum vascular the vascular layer from there the other blood vessels which go to the endometrium these are the ones that are initially affected during menstruation remember that the endometrium has two parts the stratum basales that layer is the one that remains when menstruation takes place and starting functionalists this one this is the one that is shared off when menstruation took place during implantation the concept has been borrowed through the stratum functionalist up to there the junction between stratum functionalists and stratum basales that is the normal extent of the borrowing okay i want to give you a question the question is projected again i want you to think through it and make a decision around it you have 30 seconds now we can proceed [Music] having talked about what implantation is and talked about the normal site of implantation let's now outline the key steps that take place during the process of implantation one of the first things that must take place is actually the hatching process so consider hatching the first event towards the implantation because if the blastocyst does not hatch then there will be no implantation remember hatching actually takes place towards the latter end of the first week of development that means that actually implantation begins at the end or towards the end of the first week of development but most of the events will then be carried through the second week of development we defined hatching as extrusion of the blastocyst from the shell of the zona pellucida and uh we said that during hatching the embryonic pull of the blastocyst is the one that leads the way hatching occurs when the blastocyst arrives within the endometrial cavity so usually around day five day six there as you can see in this image as the shell of the zona pellucida is the blastocyst and it's the abimbranic pole that has led the way after the blastocyst has hatched it will then attach onto the endometrial lining so we call that attachment the blastocyst attaches onto the endometrial lining using the embryonic pole of the blastocyst the site where the blastocyst will actually attach will determine where the placenta will actually be formed the site of attachment determines the site of placentation normally as i told you this attachment within the upper part of the turn segments and so most of the time the placenta will be thunder anterior or fungal posterior after the attachment there's a layer of the trophoblast that now differentiate but let me put it this way the trophoblast differentiates into two layers after the attachment there's an outer layer where the cells don't seem to have definite cell boundaries you see a nucleus you see another one and you don't see a boundary it appears like the cells are fused we call that layer the sensitive trophoblast the term sensitive from god sensitive means fused or uniform or together kind of so this is the synthetic trophoblast but there's also another layer of the trophoblast where we are still able to see the cell boundaries that is what we call the cytotrophoblast so the trophoblast differentiates into two layers outer layer called sensitive trophoblasts and inner layer called cytotrophoblasts at the implantation site we have the sensitive trophoblast forming and that is important during implantation because this sensitive trophoblast invade the endometrium it is the layer that actually burrows through the endometrium other one other than borrowing through the endometrium the sensitive trophoblast also participate in secretion of a hormone called the human chorionic gonadotropin you can call it hcg what is the role of hcg i know it's tempting for you to say that hexage is used to diagnose pregnancy well that's more of a clinical application of the biology the role of hcg is to maintain the corpus luteum so that corpus luteum can continue to produce progesterone [Music] we are going to talk about that shortly when you talk about the mono changes so for now i want to capture that after the attachment the sensitive trophoblast forms and so the sensitive trophoblast helped to borrow the endometrium and so the process of borrowing or i'm calling it invasion and embedding will go on as you can see the conceptus is now entering the endometrium this is the synthetic trophoblast now it has become it has expanded and that's the cytotrophic blast how far will it reach the junction between the stratum functionalists and the stratum vessels is a normal extent of the borrowing during that borrowing and as the sensitive trophoblasts continue to become big there are some vascular channels which appear within the trophoblast especially within the sensitive trophoblast like these ones these vascular channels are known as the trophoblastic lacunae so there are vascular channels that appear within the sensitive trophoblast trophoblastic lacking this trophoblastic lachine communicate with similar vascular channels within the endometrium which we call maternal sinusoids so we have maternal sinusoids and they have trophoblastic lacking these communicate they contain blood and so they're a form of communication which means a form of exchange of substances this primitive form of exchange of substances before the placenta is established is otherwise known as the primitive center unit so we have establishment of the primitive uteroplacental unit at this point because of that communication exchange of substances between the trophoblastic lacunae and the maternal sinusites now remember that the blastocyst created a defect on the endometrium when it was borrowing that defect that it created needed to be repaired and so that's the last towards during implantation the defect that was created now repairs itself the repair process will first occur by some fibrin clots and then you'll have the epithelium regenerating to cover the conceptus great so that's the process of implantation after the epithelium has repaired we are now sure that implantation is complete so remember i defined it as the process of invading the numerator during okay maybe that one is wrongly coined is the process by which the blastocyst invade the endometrium and that the endometrium is invaded by via the trophoblast the trophoblast layer is the one that invades the endometrium during implantation generally the process of implantation will begin on the sixth day after fertilization which means towards the end of the first week and in general it's completed by the 13th day after fertilization almost the end of the second week we generally say by the end of the second week implantation is complete so that by by the end of implantation the conceptus is two weeks old i told you that the site of implantation will determine the site of placentation some women may bleed a little some spotting when implantation is taking place we call that implantation bleeding [Music] it may occur around that time of implantation now that spotting can be easily confused with normal menstrual flow with menstrual flow but you need to distinguish that too how do we distinguish the two implantation bleeding is just spotting and so we expect it to last just less than a day remember menstrual flow will last for some three four five days and of course it's heavier but the confusion arises because this time that this woman is seeing that bleeding is almost around the same time that this woman was expecting her next menstrual because they're talking about two weeks after conception two weeks after ovulation and that's the time that she's expecting her next floor so a woman can easily confuse this with menstrual flow so if you're asking a woman then you they tell you if you ask them the last normal mainstream then they give you a date it is important that you ask how long was that flow if they tell you just a spotting then maybe that was implantation bleeding right another question for you projected take some 30 seconds and think through it okay we can proceed now so let's look at the hormonal changes that take place during implantation before we look at those hormonal changes let's understand some of the more changes that occur before implantation start from the ovary we say that the follicle stimulating hormone stimulate the ovary so that we have follicular development and so during the follicular phase of the ovary the levels of estrogen also rise and so we call that the estrogen phase it reaches a point when we have a dominant follicle that will then be ovulated around the time of ovulation we know that we have a positive feedback mechanism that causes luteinizing hormone such and that is what will eventually lead to extrusion of the oocyte from the ovary in the process of ovulation after ovulation the structure that remain in the ovary is called the corpus luteum the copper's lithium produces progesterone high levels and so we call that neutral face the progesterone phase as you can see in that image but the corpus luteum does not last forever the corpus luteum lasts for only 11 to 14 days let's call it two weeks so because the corpus luteum is going to involute it means that the levels of progesterone are going to go down as well as the levels of estrogen that has implications on the uterus let's see how so these are the hormonal faces of the ovary on your left hand side and these are the endometrial events on your right hand side when estrogen levels are rising that causes proliferation of the endometrium when the levels of progesterone are high here progesterone face that causes endometrial glands to develop and the blood vessels to become more so we call the secretory phase but when the copper's lithium disappears and so the hormonal production of the ovary go down both for estrogen and progesterone because of that hormonal deficiency we have menstruation so this is what happened before implantation the decline of the ovarian hormones will lead to menstruation in a month that the oocyte has been released ovulation has taken place but the oocyte is not fertilized the copper's determined only lasts for about two weeks because the corpus luteum involutes the hormonal production of the ovary also go down so we are looking at the levels of progesterone and estrogen we have a decline in the levels of estrogen and progesterone because of the decline in the levels of these ovarian hormones especially progesterone the secretory phase of the endometrium cannot continue it will enter into ischemic phase which will then be followed by the menstrual face if you remember the lecture on female reproductive cycles that should be clear to you so this is what happens when there is no fertilization and there's no pregnancy it's a common it's a repeated thing how about that time now that the oocyte that was released was fertilized and implantation has taken place or is taking place what are the mono changes i told you that the sensitive trophoblast will produce hcg this since its trophoblast that produces hcg is the one that was being used during implantation so it produces hcg the role of hcg is to maintain the corpus luteum so that corpus luteum does not disappear but remain in the ovary which means that continue to produce progesterone and estrogen hormone because of that sustenance of the corpus luteum and therefore continued production of estrogen and progesterone the secretory face of the endometrium or the little face of the ovary continue and because of that menstruation will not take place that phase that the endometrium enters is what you call the pregnancy phase of the endometrium so the key point to note here is that when there is implantation that is hcg that sustain the corpus to term so corpus luteum continue to supply estrogen and progesterone and for that reason there'll be no menstruation the corpus luteum of pregnancy does not also just last forever though usually it lasts for about two to three months after the two to three months the corpus luteum of pregnancy will also involute that does not mean that we no longer require estrogen and progesterone the main thing here is that now at this point the placenta has established and so it is able to produce its own progesterone and estrogen that sustain the pregnancy so those are the hormonal changes which take place during implantation now let's do the last part of the lecture let's look at some of the conditions which occur due to abnormal implantation process one of the things i want to talk about is ectopic pregnancy ectopic pregnancy is implantation hence pregnancy outside the endometrial cavity remember i told you that the normal site is endometrial cavity so if the conceptus does not implant within the endometrial cavity it is outside endometrial cavity we call that ectopic pregnancy or ectopic gestation ectopic gestation could be within the ovary so we call that ovarian pregnancy could be in the abdomen cavity or peritoneal cavity we call that peritoneal or abdominal pregnancy it could be within the fallopian tube we call that tubular pregnancy could be in the cervix and we call that cervical pregnancy the commonest form of ectopic pregnancy is tubal pregnancy over 90 percent of ectopic pregnancies are actually pregnancies within the fallopian tube now was a normal outcome of that type of ectopic pregnancy fallopian tube is relatively small significantly so actually and so it can sustain a big baby growing so if you have pregnancy in the fallopian tube as the pregnancy grows it will rupture the fallopian tube so tibor rapture is one of the outcome and if the fallopian tube ruptures then there could be some bleeding bleeding from the mother bleeding from the implantation site and that significant bleeding will then mean that the embryo will not be viable so it will actually lead to embryonic demise if you have tribal rupture you have embryonic demise and remember also the life of the mother may be at risk to some extent depending on how much blood she loses when that tube ruptures before it is picked by clinician and so some intervention done so tribal ectopic pregnancy is not something to joke around with usually when we detect tribal ectopic pregnancy you'll be told that the management is to terminate that pregnancy because of the outcome we've talked about now the other disorder of implantation is placenta previa placenta previa refers to a placenta that has formed the lower parts of the different segment like in these images you're seeing here it's a low-lying placenta well there are different degrees of placenta previa but let's look at this one which you call grade four where the placenta is obliterating the internal horse the cervical canal if this baby is to be born this placenta will have to separate fast and maybe come out before this baby can come out what's the danger of that first of all there'll be a lot of bleeding from that site of separation even before the baby is born and that is what we call anti-pattern hemorrhage bleeding before delivery of the baby other than that if you separate the placenta before the baby comes out it means that you're actually cutting off oxygen supply to the baby and so when this baby come out chances are that this baby will not be alive it will be a stillbirth so again the normal management of this kind of placenta previa which you call grade four placenta previa is basically a caesarean section so that the baby is delivered from this side okay the other dissolution of implantation is where the conceptus has invaded too deep into the uterine wall let's use these images to remind ourselves of the layers of the twin wall so the endometrium myometrium and perimetrium we say that the endometrium has two zones stratum functionalis and stratum basales the normal implantation is where the placenta is reaching that junction there because that is where the invasion reached the junction instead of functionalist basal is there so you may have a scenario where the invention was beyond the whole of the enumeration like this we call that placenta a crater you may also have a scenario where it invaded too deep into the muscular layer that's what we call the placenta in crater and the last one and most extreme is where it goes through all the layers of the eaten wall we call that placenta per creta of course this is with increasing severity was a problem with this kind of placentation or placental attachment such placenta will not come out easily after the baby is born so it will give us what we call retained placentation when the placenta refuses to come out yet the baby has been born we call that return placenta and it has its own challenges one of them being the risk of a lot of bleeding after delivery what we now call postpartum hemorrhage okay one last thing is that you may have early pregnancy loss or you call it early pregnancy failure the term pregnancy loss sometimes called miscarriage or spontaneous abortion is generally defined as an unviable pregnancy up to 20 weeks of gestation so basically the first half of the pregnancy if the baby is not viable we are looking at the viability of the baby if the baby is not verb which means the baby's dead basically that's a pregnancy loss so you can call it miscarriage or spontaneous abortion so when do we call it early pregnancy we call it early pregnancy loss if this loss is occurring in the first trimester remember you can divide pregnancy into three the first trimester being the first 12 weeks plus six days that's the first trimester of pregnancy and the dating system i'm using right now is the dating based on the last normal menstrual period which means that when we say that implantation is completed by the second week according to pregnancy dating now that is fourth week remember you need to add to when you are looking at embryonic or conceptual dating and you're looking at the pregnancy dating in terms of the last normal menstrual period okay now the commonest type of early pregnancy loss would be so the commonest type of pregnancy loss will be early pregnancy loss the risk factors for early pregnancy loss is numerous maybe there's some unemployed syndromes remember the trisomies and the monosomias those ones could lead to early pregnancy loss some of them could be hormonal disorders for example if the progesterone levels are just very low maybe this human chronic gonadotropic moon is not supporting the corpus luteum adequately and so the levels of progesterone are low maybe there's some infections maybe the woman conceived and she had an iucd so it's still inside there maybe she has taken some drugs these drugs that you can actually administer maybe the substance abuse maybe alcohol cigarette perhaps the woman is just super stressed obesity diabetes the least is actually endless but let's remember the first three these are the common causes of early pregnancy laws or let me not say cause but risk factors for early pregnancy loss the symptoms for early pregnancy laws have been unspecific so when you see them you can't really conclude you may have to do some other tests to for it to confirm but they'll include vaginal bleeding and perhaps some lower abdominal pain which come from mutant cramping when you use the term early pregnancy laws there's some two terminologies that you need to be familiar with and maybe one of them is what applies now and another one we'll use later so it could be a scenario where yes the conceptus is there but the inner cell mass is non-viable which means that the embryonic tissue is non-viable yet the trophoblast is still intact that is what we call the embryonic pregnancy so brought to context that is actually what i wanted to talk about as one of these disorders it may happen during the implantation process that you may have an embryonic pregnancy during the implantation process but again remember that implantation could be occurring but there's no enough levels of hormones and so it doesn't attach properly it comes out as well but later on you there's some terminologies that we can also use maybe now not necessarily during the implantation itself but after implantation has taken place maybe by imaging we see that this pregnancy [Music] and we see the baby but we don't see the cardiac activity the heart is not beating so when the heart is not beating we call it embryonic demise or fetal demise depending on the timing you know the fetus will be an older one and the embryo is a younger one so the term embryonic demise or fetal demise still constitute part of what you call the early pregnancy laws there's a term that you may come across in your books we call it blighted ovum that term is a historical phrase but it basically refers to embryonic pregnancy pregnancy where the trophoblastic tissue is still there but the inner cell mass isn't non-viable and so that baby is not going to proceeding great these are the disorders of implantation and so we will stop there the next lecture will be on the events of the second week of development now excluding the process of implantation you