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Where does Embryo Implantation occur?

Where does Embryo Implantation occur?


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Where does the embryo get implanted? If it is in the uterus side wall, why is the embryo shown hanging from top in some pictures?


According to Minami et al. (2003)1 (open access) the early gestational sac can be located by ultrasound, and usually is high in the uterus, more often on the left or right than in the middle. They provide an illustration of the distribution.


1. Minami, S., Ishihara, K. and Araki, T., 2003. Determination of blastocyst implantation site in spontaneous pregnancies using three-dimensional transvaginal ultrasound. Journal of Nippon Medical School, 70(3), pp.250-254.


Where does Embryo Implantation occur? - Biology

Once the zygote implants in the uterine wall, embryonic and fetal development continue through three trimesters to birth.

Learning Objectives

Describe the development of the human fetus from fertilization through the third trimester

Key Takeaways

Key Points

  • After fertilization, the zygote implants itself in the uterine wall its outer layer grows into the endometrium, where it begins to produce human chorionic gonadotropin.
  • During the first trimester, the placenta forms along with the internal organs and structures however, not all of the internal organs function at this point.
  • During the second trimester, internal organs continue to develop and the fetus becomes active.
  • The third trimester is one of rapid growth, in which the fetus reaches its full size pregnancy often becomes uncomfortable for the mother.

Key Terms

  • zygote: a diploid fertilized egg cell
  • chorion: allows exchange of oxygen and carbon dioxide between the embryo and the egg’s external environment
  • human chorionic gonadotropin: a peptide hormone, produced during pregnancy, that prevents the breakdown of the corpus luteum and maintains progesterone production
  • placenta: a vascular organ in mammals that supplies food and oxygen from the mother to the fetus, while passing back waste it is implanted in the wall of the uterus

Human gestation

Twenty-four hours before fertilization, the egg has finished meiosis and become a mature oocyte. When fertilized (at conception), the egg, now known as a zygote, travels through the oviduct to the uterus. The developing embryo must implant into the wall of the uterus within seven days or it will deteriorate and die. The outer layers of the zygote ( blastocyst ) grow into the endometrium by digesting the endometrial cells. Wound healing of the endometrium closes up the blastocyst into the tissue. Another layer of the blastocyst, the chorion, begins releasing a hormone called human chorionic gonadotropin (hCG) which makes its way to the corpus luteum, keeping it active. This ensures adequate levels of progesterone that will maintain the endometrium of the uterus for the support of the developing embryo. Pregnancy tests determine the level of hCG in urine or serum: if the hormone is present, the test is positive.

Development of the embryo: In humans, fertilization occurs soon after the oocyte leaves the ovary. Implantation occurs eight or nine days later. The embryo divides several times as it travels.

First trimester

The gestation period is divided into three equal periods or trimesters. During the first two to four weeks of the first trimester, nutrition and waste are handled by the endometrial lining through diffusion. As the trimester progresses, the outer layer of the embryo begins to merge with the endometrium and the placenta forms. This organ takes over the nutrient and waste requirements of the embryo and fetus, with the mother’s blood passing nutrients to the placenta and removing waste from it. Chemicals from the fetus, such as bilirubin, are processed by the mother’s liver for elimination. Some of the mother’s immunoglobulins will pass through the placenta, providing passive immunity against some potential infections.

Internal organs and body structures begin to develop during the first trimester. By five weeks, limb buds, eyes, the heart, and liver have been basically formed. By eight weeks, the term fetus applies the body is essentially formed. The individual is about five centimeters (two inches) in length and many of the organs, such as the lungs and liver, are not yet functioning. Exposure to any toxins is especially dangerous during the first trimester, as all of the body’s organs and structures are going through initial development. Anything that affects that development can have a severe effect on the fetus’ survival.

First trimester: Fetal development is shown at nine weeks gestation. At this stage, the body is essentially formed however many of the organs are not yet functioning.

Second trimester

During the second trimester, the fetus grows to about 30 cm (12 inches). As it becomes active, the mother usually feels the first movements. All organs and structures continue to develop. The placenta has taken over the functions of nutrition and waste, along with the production of estrogen and progesterone from the corpus luteum, which has degenerated. The placenta will continue functioning up through the delivery of the fetus.

Second trimester: This fetus is just entering the second trimester, when the placenta takes over more of the functions performed as the baby develops.

Third trimester

During the third trimester, the fetus grows to 3 to 4 kg (6 ½ -8 ½ lbs.) and about 50 cm (19-20 inches) long. This is the period of the most rapid growth during the pregnancy. Organ development continues to birth (and some systems, such as the nervous system and liver, continue to develop after birth). The mother will be at her most uncomfortable during this trimester. She may urinate frequently due to pressure on the bladder from the fetus. There may also be intestinal blockage and circulatory problems, especially in her legs. Clots may form in her legs due to pressure from the fetus on returning veins as they enter the abdominal cavity.


1. Ovulation

What is Ovulation?

Ovulation is the release of a mature egg from the ovary for potential fertilization. Without the egg release on ovulation day, natural conception could never take place.

Normally, numerous eggs are maturing in both ovaries, but only one is released per ovulation cycle. If two or more are released and fertilized, pregnancy with twins or triplets can ensue.

When does Ovulation Occur?

Ovulation occurs on a monthly basis roughly in the middle of a woman's menstrual cycle, or two weeks before her next period.

There are numerous helpful tools, such as ovulation tests or ovulation predictors, which can help women estimate their ovulation date to make conception efforts more productive.

Where does Ovulation Occur?

The egg is released into one of the fallopian tubes, parts of the female reproductive system that connect the ovaries with the uterus, which is where ovulation occurs. Fallopian tubes are also called oviducts.

For How Long does Ovulation Last?

Ovulation lasts for about 12 to 24 hours. It is the only time during which the egg can be fertilized if sperm are also present in the oviduct. Otherwise, an unfertilized egg will travel to the uterus to be disintegrated and shed during the next period, roughly two weeks later.


What happens during and after implantation?

Implantation is a stage of pregnancy where the embryo attaches itself to the walls of the uterus. For couples who have undergone a form of Assisted Reproductive Technology (ART), the embryo is formed externally under favourable conditions in the laboratory. After the embryo is formed, it is cultured under observation to determine if it is healthy and has the potential to cause a successful pregnancy.
The next stage involves transferring the embryo into the uterine cavity where the embryo is expected to attach itself to the lining of the uterus after further development.

When Does Implantation Symptoms Start?

Implantation, typically, occurs 7-12 days after conception. The cells start to divide in the embryo, developing into a zygote. The zygote implants itself to the uterine walls. As soon as implantation is completed, the zygote releases a hormone called hcG, which is used by pregnancy tests to determine pregnancy.

Common Symptoms of Implantation

The first sign of implantation is implantation bleeding which occurs 6-12 days post conception. If the implantation is successful, spotting or light cramping can be experienced. If unsuccessful, your period will start. Some of the common post embryo implantation symptoms are listed below:

  • Cramping and spotting: A brown vaginal discharge for 1-2 days is experienced after a successful implantation. Some women may also experience cramping on the days during implantation.
  • Breast discomfort: Tenderness of the breasts can be experienced along with light swelling. It will last a few days during ovulation which is persistent in case of a pregnant woman.
  • Changes in food preference: Some women experience an elevation in their olfactory senses or sensation of taste, causing aversions to certain types of foods or intense cravings. This is caused due to the alterations of hormonal levels.
  • Temperature changes: A slight increase in body temperature is commonly experienced due to elevated levels of progesterone.

Symptoms such as acne, constipation, fatigue or morning sickness are also common in some cases.

The Right Time to Perform a Pregnancy Test

As pregnancy tests measure the hcG hormone released by the zygote, which increases after every 2-3 days. It can, however, take up to 3 or 4 weeks for a detectable amount of hcG to be released. A pregnancy test can be administered at home for a preliminary result and has to be confirmed with the help of a blood test performed by a doctor.

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I had 5day blast transfer on the 4th of match. On my bed rest. Hoping I have a positive result at the end of 2ww

Has anyone here had spotting 6 days after day5 fet? It’s peach-ish in color which stood out against the huge blob of pale yellowish Crinone stuff it came out with. Didn’t see anything like it during our 1st failed transfer.

What was your outcome as I have just experienced this symptom with the pinkish blood amongst the small discharge of crinone. I had a miscarriage last month but didn’t have any symptoms like this.
Look forward to hearing positive news.
Megan

Hello everyone,
I had a transfer on tue, 10/12. 4BC and 3BC
Tried to read about the quality of these embryos but I’m confused, anybody have any success with these type? It’s FET, had OHSS and had to freeze. Now transferred and waiting for 2wks to do PT.

Good luck ladies, will appreciate quick responses.

I just had my second FET last 2 weeks. Tomorrow will be the end of the 2ww and will be doing the bhcg test. But I started having little spotting since 2 days ago..hope all is well.

today is my first day after 5dtransfer of 2 embryo a blasto and not to good embryo. the problem is it needs to be PGD tested but they didnt reach the proper day so i did a fresh transfer. My DH has known balanced translocation (2,19).. what is the probability that it can be succesful? any success stories that you guys may know, to lift up my sanity?

Asma hows your bhcg?? Hoping you got a BFP.

This is my second IVF.I did one sometimes in September of 2018 and it did not succeed. I had my 5 days transfer on 5/14/19.2 embryos transferred.Today is the 3 day and i can’t say am feeling anything as of now.Just keeping my fingers cross while praying and hoping.I know its going to be a very long two weeks wait.

Asma i had same like u. 10th day of fet i bleed a little with cramping. 23rd is my bhcg test date. What about ur result?

Hello, my husband and I have only one embryo frozen (day 6) and its being transferred into my our surrogate in a few weeks. I’m so nervous only having one, means only once chance. Are there decent success rates with day 6 emrbyos? Anything we can do to enhance implantation? Do all frozen embryos thaw ?

Hi Happymessyme… thanks a lot… we both are on same dates(17.18)best wishes for your little one… yea it is very crucial time may God succeed us with all those who are trying.dont be panic this is good sign that you feel mild cramping. I m still feel nothing …. may b it is too early now.update me about your condition.

Hi all ivfers….. I have put in back one healthy embryo On 17 April… and now on my rest daysbut very anxious becos of my miscarriage in December 18.may God protect our little onesgood luck for all ivfers.

Sending you lots of sticky baby dust. I had my transfer a day after yours on 18th April. I am so tensed as I have started having mild cramps. I always get these cramps and get my periods even before tww ends. I hope this one doesn’t end the same way. 5 years of ttc, I really wanna see those two pink lines and have a healthy baby. Hope we both get a bfp soon and sorry about the rant.

Hi every one, I had my 3 day embryo transfer on 11th of April, am having slight waist pain, l hope all is well. I don’t know how to cope with this 2weeks wait. God help me pleeease

Hi there, I had my transfer on April 14th. I am experiencing some lower pelvic discomfort as well. My prayers are with you too! The wait is arrrrg. Best of luck and many blessings on this journey.

I had 2 transferred day before you on 10th. I had pelvic discomfort when sneezing. U think it’s implantation related? Wish there were clearer symptoms. Praying 4 blessings!

Same applies to me i had same issue 3 day transfer how did it go with u

How did your 3 day transfer workout?

Hi please let me know if I missed period after embryo transfer does it mean I am pregnant .

In failed embryo implantation when do periods start? Do it start on last cycle date only or get delayed due to ivf process.

It usually comes a little later. Can be as late as 2 weeks after the process has ended.

Hello ladies
I am currently on my 3rd cycle. This one is a 5 day blast that was hatching. It’s a grade 6bb. All the tests looked good prior to implantation but with 2 failed I’m trying very hard to keep a positive outlook. BABY DUST to you all!! I will let you know what happens.

Heading to the hospital now to have my rainbow boy!

Congratulations! On the day 12 of my 2ww, tensed, anxious, nervous and at the same time scared. This is my fourth ivf cycle

I am 27, I had my egg retrieval 3/26/19 and had 5 blastocyst Day 5 and 2 blastocyst Day 6. I had to freeze all 7 embryos because of risk of OHSS now on the final stages of natural cycle egg transfer. My question for the ladies who have had the egg transfer is what were the measurements of LH level and P4 level along with measurement of lining of uterus currently the I had 2 ultrasounds and bloodwork

LH 22.81 04/03/2019
LH 15.01 04/05/2019

P4 0.098 04/03/2019
P4 0.080 04/05/2019

Latest 4/05/2019 lining was 7.5mm

I am 39 as of yesterday, and today 4/3/19 we implanted 2 day 5 blastocysts. We have 3, a 5AB, a 4AA, and a 4BB. With my age, we chose to go with the best and the worst (4AA and 4BB). We do not want twins, but we can not afford to do this again. We will find out next Friday if we are positive, and the May 6th will be a sonogram to confirm 1 or 2 if everything goes well. I will try and update when we know more. Hopefully it will help someone else be able to make the choice of 1 or 2

I had my transfer the same day as you and won’t know my results until Sunday.

Hi dear
How are you doing! Did you conceive thro this cycle of ivf

I am 35 very fertile and according to my doctor perfect lineing. my transfer is march 18, 2019 and my egg retrieval is this coming march 13, 2019. I’m doing a fresh transfer embryo and I only get this one shot chance since I had my tubes tied and I can’t afford freezing my eggs. doctor said I should consider putting in two embryos but I don’t want twins I can’t handle them both as I already have twins from a natural pregnancy and now I’m newly re married and this is the only chance I have at getting pregnant. I’m really scared to loose my chance so I don’t know what my chances are that the one embryo we pick implants correctly? I’m really nervous and can’t sleep over this topic whether I go with two embryos or one. thank you so much for your help

I was wodering how was your outcome didnyou get a BFP

Dear Kelly,
I was moved by many of the stories here but mostly with yours just because we are a week apart in our IVF cycle’s events. Our egg collection was last Friday, 22nd of March and embryo transfer on Monday 25th. We originally had 3 embryos, lost 1 so have decided with my husband and doctors to transfer the remaining 2 even though I was a bit concerned about the twins possibility, I am only 48kg but I am 40 in a few days time so took the risk. What did you do? And most important have you got your result now? Sending you positive thoughts, Andreea

Hi everyone,am 33, my egg retrieval was done on 17/3/2019 and my day 5 egg transfer was perform on 22/3/2019 .surprised at of the 11 eggs i had,two was fully mature but was very weak according to my doctor,but was managed to sustain it till the day five ,which was transfer successfully, today been my 7days of my egg transfer had a bleeding kind of spotting and a little cramp on my Tommy.pls could it be that am on the positive side.thanks

Hi everyone, I’m transferring my first embryo on weds and I’m trying so hard to balance being informed and prepared with string relaxed and open so that stress doesn’t become a problem.

Reading your experiences is so helpful. Thank you for sharing.

I really hope your doing great. I would to know if any update on you IVF?

I am doing mine tomorrow and I am kind exited and nervous at the same time.

Hello everyone, I had my 3 days embryo transfer on Thursday. I’m trying to relax but I’m honestly very stressed. The wait is driving me crazy. I’m 42 and this is my second IVF. I could produce any good egg on my first cycle, but now I produced only one. I don’t know how am I gonna wait till the 18th of the month.

Hi I had my embryo transfer on Wednesday. it is now Sunday so it’s day 4 today counting Wednesday as day 0. last night I had cramps, bloating and was really upset over nothing on particular. no signs of spotting yet.

Hi Lisa, how’s everything? I did my transfer 1/24 and did my fist beta 2/1. Doc called me yesterday and informed me that I’m negative. I was in shock. I stopped meds last night. Period is supplying come today but I guess I have to wait 3 days since I still have meds in my system. I don’t know what happened. We transferred 4AA . I was hoping it will implant . I don’t know what went wrong . Anyways hope u have a good implant and BfP .

Hi. I had a transfer on Monday 7th Jan 2019. I notice blood in my urine yesternight. But none again since last nite. Is that spotting or what?

How did you get on after your slight bleed?? Everything ok?? I had my transfer yesterday, it’s my 2nd time round and I’m so worried it’s not going to work again

I am 39 just had my 5 day transfer. Dr implanted 2 embryos and I froze 2 so now the wait begins, I feel very good about this, it’s our first time after ttc for almost 2 years and 2 failed iui. I wish everyone the best!!

Hi I’m 44 and I have my embryo transfer on monday and I’m on day 7 of the 2ww waiting but I haven’t gotten and bleeding does that mean it hasnt worked this my second go already and I’ve got four more days before my blood test on Thursday could any one help plz I’m worried that it hasnt worked again

Hey Carla,
I was on here checking when I can safely do a HPT as I am day 5 after FET. I am so glad a stumbled onto your question. Blood/spotting could be a good sign, but could also be a bad sign. Cramping COULD be a good sign, but could also be a bad sign. I would say just rest and enjoy this time with your little embryo! I would also say based on what I have read that you may be able to test positive on a HPT by now. So as long as that won’t worry you more, give it a shot!! Have fun!!

Good luck to you! The waiting is so stressful! I had my FET on 10 Dec and just had my bloodwork done today. Positive for pregnancy. But very low hCG levels and cramping so now I’m stressing about that.

Hi – got same thing going . just had transfer yesterday

Hi. I’m 40 and I’m on day 9 after my transfer. I go tomorrow for blood work but I too have not had any bleeding. I’m worried as well if that means it did not work. I did have cramping though. This is our second try and we did not get this far the first time. They retrieved 19 follicles total with both retreivals, and 14 fertilized, and 6 made it to day 5 for testing and 1 made it to transfer. It is a lot to swallow when I look at the numbers. Good luck to you. I hope everything works out and you guys get a beautiful blessin.

Hi I am 44 as well and had my transfer on 1/16. On bed rest right now… How did yours go?? Are you pregnant?

Hey Carla,
I’ve just had my 4th transfer, so I am in Professional Chill mode atm. The way I see it, we can’t know anything until ew get the pregnancy test results (blood tests), and tempting though it is, some women have blood spotting, some don’t, some women cramp, some don’t the only certainty is the blood test.
I wish you and all the other women on this thread (including myself!) every success on this journey.

Did you do pgs or fresh transfer.

I’m curious as to how it turned out?

Hi I’m 44 and I have my embryo transfer on monday and I’m on day 7 of the 2ww waiting but I haven’t gotten and bleeding does that mean it hasnt worked this my second go already and I’ve got four more days before my blood test on Thursday

Putting in 2 blastocysts is very risky- it may be more likely to result in a pregnancy but the risks of having twins including pre-term birth, miscarriage, twin to twin transfusion are so much higher and generally not worth the risk.

I’m 43 and had tubes tied 13 years ago but my husband and I want another baby. Prior to me getting my tubes tied I was very fertile , is that a good thing? I’m not sure IVF is right for us any suggestions .

If you had your tubes tied, IVF is perfect. You won’t need those tubes because they’ll take eggs directly from mature follicles on your ovaries.

I did the same thing after our daughter in 2012 and we have just had our first transfer. Don’t be worried! Go for it. Good luck xxxx

I just went through IVF, after having my tubes tied 6 years ago! I had my transfer yesterday, now just in the waiting period to see if it worked! I don’t feel like IVF was as time consuming or as scary as I thought it was going to be! Other than paying more than $12,000… I would recommend it to anyone that can’t conceive on their own… they did give me the option to untie my tubes, but said it would be about the same cost, and that doesn’t always work either.

I am 45 had a tubal reversal a year ago and 4 months ago i was prgnant naturally but had a miscarried at 7 weeks 2 months after that nothing happens so we decided to for IVF but the doc said because of age my eggs are 45 years old and that chances being pregnant are about 2% so we decided to go for donor eggs… after 2 months on meds my body is ready for a transfer on 01/10/19 ii am very nervous and cant wait for a pregnancy test.. good luck to you and all plz keep posted

I had IVF surgery today. It was my first time. I didn’t know it would be so emotionally tough. I am 40 just! I waited for the right man and got proffessional qualifications, did it all the right way for me. I was told that i had 9 possible folicules they would extract. Very nervous of the GA i walked upto surgery and after some tears they put me under. I awoke to a surgeon saying you can wake up now. My first words were is everything alright? Yes we got 7 healthy looking folicules. Feeling very pleased i was sure everything would be alright. I went back to my room and waited for news from the embrologist. They arrived in my room to tell me 6 of the folicules had not matured but they were waiting to see if the remaining one would continue to mature. We were devistated. I had no idea that this could happen. 3 hrs later there was hope. The egg had continued to mature and so now we are waiting to see if it will fertalise. I have come on here looking for advice, solice and answers. If it does fertalise they said they would implant it after 3 days. I know this is a 1 in 8 chance of succeding. What is the best thing to do. Should i stay at home and not move around?

Hi,
So at 40 I started IVF after 2 years of trying naturally. The clinic suggested I purchase 3 rounds which sounded crazy to me. I was 40 and a half at this point but we reluctantly agreed. Well..5 cycles later we have 2 genetically viable embryos and probably 9 that made it to maturity but tested abnormally. Today I did my first transfer so fingers crossed. I guess what I have realized through this is that it might (at least it was for me) not as easy as I expected and obviously ended up costing us a lot more money but you are only 40 so if it is at all possible to do another round, better now than later. I went through 5 straight months of IVF cycles which was probably the hardest thing I have done but hopefully we will now have at least one healthy baby. Every cycle yielded such different results, you could do one more and it could be your success so please don’t give up hope!!

Right now, the best thing to do is to relax and not worry. We’re on the same page right now. Just trust the professionals and be as positive as you could be.
Everything happens for a reason, and I believe that when it’s time to happen… it will happen.

HI all, i am on my 10th day after embryo transfered and i sow blood today when i wake up, is there any one expeirienced on this, do i need still to do the urine test? please advise?

That’s precisely what’s happened to me, how did it go for you?

My husband and i are doing ICSI and this is our first attempt. Today Monday being 11/06/2018 I just receive my transfer embryo, of which my eggs was taken on Friday the 8/06/2018.
However, I have no pains, no cramps, no bloating. But I feel bubbling gas in my stomach that makes me wanna fart…(Am Shy saying this).
Dr my question is, Is this normal or something i have to worry about?
Also, do I need to continue drinking lots of water like I used to?
I usually take FLAXSEED/LINSEED AND THE OIL. And Apple Cider Vinegar (ACV), should I stop taking them?
What tea is best to drink at this time?
Please any more or additional advice on how I should behave or handle this situation?
I will really appreciate your candid advice.
Looking forward. Thank you and God bless.
Queen .E. Tomei

Hi ladies! I am 39 (40 in 2 months ) and have been TTC x past 2.5 years. First naturally, then discovered 6 months later that I had bilateral hydrospinx (tubal occlusion). I was told our only chance for conceiving would be with IVF and even then only after bilateral tubal removal which I did shortly after consult. Otherwise docs always say my numbers look great (initial evaluation in 2016 showed AMH 4.0, low FSH, high antral follicle count for my age). Soooo with all those better than average stats I went into IVF with the attitude that it would be a cake walk and I would knock it out of the park the first round. After my tubal surgery I took a break thinking it would be best to allow my body to heal before attempting IVF and to be quite honest I was still on the fence about the whole thing. I hate taking medications and was conflicted about conceiving a child this way.. my concerns over the eventual wellbeing and health of a child that is the product of IVF vs nature. Fast forward 10 months later and I finally worked up the courage to go for it and try IVF. When we retested my labs, AMH had taken quite a nose dive (from 4.0 to 2.7) which is significant drop in the world of AMH. My doc said this could be attributed to increase in age (I was now 39, and effects of tubal surgery). Again being the naturalist and wanting to keep things as close to nature as possible I opted for natural cycle IVF, a single egg was retrieved using no stimulation meds only HCG trigger to induce ovulation. That egg did not fertilize (this could be due to the fact that we totally mistimed the shot due to air travel as we were flying cross country to see a specialist in natural cycle). Next month we decided to try again this time at a fertility clinic in our hometown. Natural cycle again, this time retrieved one egg, it fertilized, developed into a perfect 3D grade A embryo which was transferred back on day 3 (due to the fact you only get 1-2 eggs with natural cycle they always perform day 3 transfers). This embie took and I had implantation cramps, crazy hormonal swings etc about 2 days after transfer. This pregnancy was unfortunately a chemical and ended in MC at 4 weeks. First MC and boy was it painful and I’m pretty tough! Next round of natural cycle ra couple months later.. retrieved 2 eggs, transferred a very perfect looking compacted morula and a 7 cell grade A embryo back on day 3. During the 2WW absolutely zero prego symptoms, implantation cramps like the first. This ended in a BFN. After this 3rd unsuccessful attempt at natural cycle our RE convinced us that even though my numbers all look amazing for my age, we were likely dealing with egg quality issues due to my age which was causing embryos to fail. He wisely knowing how much I hate meds suggested we try “mini IVF” to hopefully increase our odds of achieving pregnancy. We decided since time has been slipping away and I’m not getting any younger to first do a freeze all cycle to have some 39 yo eggs for later use and then do another back to back cycle with a fresh transfer. Let me tell you Mini IVF is no big deal at all. I took an oral med called letrozole for the first 3 days to suppress estrogen release to allow more than the usual 1-2 eggs to recruit and then took gonal-F (FSH) injectable one time a day until follicles were looking big enough then took cetrotide (suppresses LH and thereby blocks spontaneous ovulation) for a couple days untold we were ready to trigger. First cycle we retrieved 8 eggs, 6 fertilized with standard IVF (no ICSI- again I like to keep it as natural as possible and we do not have sperm issues), and 2 made it blast stage and we’re good enough to freeze (1 expanded 3AA blast and 1 5AA hatching blast). I’m currently in the second mini IVF cycle and did same protocol (went right in without a break) this time there were 16 follicles, retrieved 10, 8 mature, 5 fertilizer with standard IVF. Just went in today for transfer and we decided to transfer one 3AA expanded blast (agreed to assisted hatching due to my age) and froze 1 5BA hatching blast. We have 3 more early blasts which are being cultured until tomorrow and we’ll see if they make it to expanded so they too can be frozen for later use. Soooo I’m currently PUPO and in the dreaded 2WW. But I have to say, after so many failed attempts even with “better than average” stats for my age, I am super non-chalant about the whole thing. Yes I am doing my Dr’s recommended 48 HR bed rest and taking my vivelle for every 72H and my crinone 8% every morning and my medrol twice a day and prenatals and my usual slew of supplements (DHA and vitamin D3 are SUPER important for healthy fetal development!) but I’m not stressing this time cuz I’m used to failure and I’ve settled in with the idea now that 39 year old eggs are probably mostly bad lol. I do have hope that eventually we will get that one superstar who will hang in there the whole 9 months and that gives me realistic hope! I have learned the hard way not to be overly optimistic or obsessive or stressed cuz this is truly our of our hands! It’s nature doing what it dies best and we just sit back and wait and hope for a miracle cuz when you think about it IVF is truly a miracle indeed. I refuse to obsess over symptoms, lack of symptoms etc during this 2WW and when my obligatory bedrest is up I’m going back to doing my usual routine until the beta on 4/3. Oh and btw I also REFUSE to fall into the POAS trap because that is just uneccesary sadness when it comes back negative but you still hold out hope for the beta only to be saddened and disappointed again. So my personal rule is just wait.. better to get good or bad news only once makes it more special that way and less stressful if you get a negative. Will keep y’all posted on my results! Baby dust to all of you out there I have learned the hard way how emotionally, physically, mentally exhausting this process truly is! Stay strong ladies and believe in miracles!! They do exist, some just come when they feel like it not when we want them to

Thank you for sharing your journey. I am laying in bed after having 2 embryos tranferred today. I didn’t have any to freeze. I am hopeful one of these, stick.
Good luck with everything..

I am in bed after, a 2 embryo transfer yesterday. I am 42 years old and have been married to my husband for 12 years. I have 4 healthy adult children but 20 years ago had a tubal ligation. I pray and all God for his blessings and his wonderful miracle of life once again. Trying not to focus or allow negative mopie thoughts. Reading your posts helps me. And i wish the best for you all. **BABY DUST**…. I LOVE THAT….

I’m dying for an update. Hope it took!! I’ve had a long fertility road myself. It took 2 years and 8 IUIs to have our sweet daughter. She’s 2 now and decided it was time for another, I’m also 35. We did 4 IUIs and none of them took. It was very frustrating because it worked before. We decided so switch to IVF. I had 15 retrieved, 14 mature and fertilized. Only six made it to blast, we froze them all. Then we took a month off to give time for my body to heal. We just transfer 2 embryos 4/30. The wait is sooooo hard! I’m overanalyzing every symptom


Contents

Preimplantation factor has a simple primary peptide structure with a 15 amino acid sequence (MVRIKPGSANKPSDD). [17]

As the regulation of the maternal immune system is a requisite for successful implantation, the immune system shows different characteristics in pregnant women and non-pregnant women. In 1994, preimplantation factor was isolated by a lymphocyte platelet-binding assay that compared immune responses and proteins found in pregnant women and non-pregnant women. [4] The assay also compared immune responses with men to verify if the proteins were specific to female reproductive tissues. [4] Results generated in the preliminary study showed that "a preimplantation factor" was being expressed exclusively in pregnant women. [4] On the fourth day after embryo transfer in women who had undergone successful in-vitro fertilisation, this protein was also found, suggesting that it had a role in the determination of the viability of the embryo. [4] Subsequent studies, most seminally including a 1996 study that partially characterised the biological activity of PIF, adopted and established the current term "preimplantation factor" as the name for this novel peptide. [5]

Trophoblast invasion and adhesion Edit

Trophoblast cells form the outer lining of the blastocyst in preimplantation development, eventually forming more differentiated extra-embryonic tissues including the placenta. [18] Before this differentiation can occur the embryo's invasion and infiltration into the uterine wall must be tightly regulated by both maternal and foetal signals, including secretion of PIF by trophoblast cells. [19] In particular, preimplantation factor is thought to have a paracrine effect on the decidualisation process, which ultimately primes trophoblast cells to invade appropriately into the endometrium. [1] When compared to non-functional short peptides at the same concentration, application of PIF to the endometrium at the implantation stage promoted deeper invasion of the embryo. [1] This effect was not observed to occur indefinitely with successive increases of concentration and any artificial increases of PIF above the human physiological concentration (approximately 50 nmol/L) did not meaningfully increase the invasion of the embryo. [1] Consequently, it is thought that PIF is limited in its promotion of trophoblast invasion by maternal signals. [1] [11]

The outermost layer of the uterine wall is an epithelial tissue called the endometrium that requires cell surface adhesion molecules called integrins to adhere the embryo. This additional paracrine effect of PIF has been shown to increase the expression of the integrin molecule α2β3 on the cell membranes of cells in the endometrium. [9] Integrins are a broad class of cell adhesion molecules that allow cells to bind to extracellular matrix. [9] In this way, they assist the entire embryo in binding to the uterine wall, an important event in successfully generating a placenta. [9]

Maternal immune tolerance Edit

The embryo is immunologically characterised as a partial allograft as it is not a maternal tissue. [2] [10] During fertilisation, a paternal spermatozoon fuses with a maternal oocyte producing a zygote. Phenotypically, the zygote expresses certain epitopes that are controlled by genes inherited from the father, making the embryo a foreign material. In order for successful implantation to occur, the maternal immune system must tolerate the presence of the embryo while not completely inactivating its innate responsiveness to foreign pathogens. This process is not always successful indeed maternal immune rejection of the embryo is a common and well-characterised cause of recurrent pregnancy loss. [15]

Preimplantation factor has a significant role in signalling this grafting behaviour it has been, for instance shown to signal an anti-inflammatory response in a broad range of peripheral blood mononuclear cells. [2] PIF also impacts similar cytoskeletal proteins in CD14+, CD8+ and CD4+ cells suggesting that they have a broad and integrative role in modulating the immune system of the mother. [20] In particular, PIF inhibits the process of platelet aggregation in helper T lymphocytes and skeletal proteins in cytotoxic T cells. [20] While PIF attenuates or modulates the immune system, it does not effect the response to other pathogens or foreign material. [10] This modulatory effect on immunological tolerance is responsible for a strong correlation between PIF expression and the viability of pregnancy. [3]

Viability of pregnancy Edit

The expression of preimplantation factor in the embryo is strongly correlated with the likelihood of a live birth. [3] [20] This observed viability is not solely due to PIF's ability to mediate the implantation and allografting process but also due to its ability to promote the upregulation and integrity of certain intracellular targets that are positively associated with normal developmental processes. [20] For instance, PIF is known to target the enzyme disulfide isomerase, which reduces intracellular oxidative stress and also heat-shock proteins, which are molecular chaperones that ensure proteins produced by a cell will fold into the correct conformation for their function. [21] Additionally, PIF is known to promote the production of vital cytoskeletal proteins including actin and tubulin that are required for the current morphological development of nerve axons and the viscera of vital organs. [14] Axons use circular tubulin polymers called microtubules to transport intracellular material between the cell body and the terminal bouton and require actin to form synapses. [22] They are hence important for the organisation and function of the growing immune system.

Additionally, when uterine serum from patients with recurrent pregnancy loss is applied to embryos that are positive for PIF, they display the capacity to resist the toxin and are able to survive. [21] Combined, these observations and combination of intracellular effects suggest that PIF has multifaceted impacts directed towards viable pregnancy.

Neurogenic and anti-apoptotic effects Edit

In the prenatal environment, PIF has neuroprotective impacts. It protects the growing fetus against neonatal prematurity, preventing the foetus from being delivered before adequate neural development has taken place. [6] [10] The neurogenic effects of PIF are not isolated to the prenatal environment in fact PIF is thought to have impacts throughout life. In adult models, PIF has multiple neurogenic effects: it promotes the growth of neurons and reduces neuroinflammation. [6] [10] [16] It is thought to have these impacts by modulating signalling through the ubiquitous protein kinase A and protein kinase C intracellular signalling pathways. [6] PIF also inhibits microRNA let-7, a sequence that is highly upregulated in the central nervous system. The Let-7 system has been associated with cell death in neurons, and PIF is known to inhibit this process from occurring. [8] In rats that were induced to have a hypoxic-ischemic brain injury, PIF was able to promote neuron growth, reduced detrimental responses by neuroglia and was able to generate a significant cerebral cortex volume, suggesting it could rescue rats from side effects of brain damage. [8]

PIF also has a series of anti-apoptotic impacts in human extravillous trophoblasts, mediated by the TP53 gene. [13] Apoptosis is a controlled cell death process that must not occur if a cell is to proliferate. PIF has specific anti-apoptotic impacts by reducing the phosphorylation of the p53 protein at the serine-15 residue. Without phosphorylation p53 is unstable and undergoes ubiquitylation, signalling the trophoblast and endometrial cells to degrade it in proteasomes and attenuating downstream apoptotic effects. PIF, in particular, has been correlated with increasing the expression of anti-apoptotic effector BCL2 and decreasing the expression of pro-apoptotic effector BAX. [13] BCL2, which is upregulated by PIF, ensures that cytochrome c remains within the inner mitochondrial membrane and hence does not trigger the production of an apoptosome in the cell cytosol. BAX, which is downregulated by PIF, produces transmembrane transport channels that liberate cytochrome c, triggering apoptosis. Collectively, these biochemical effects show that PIF signals against the internal mechanisms of apoptosis in extravillous trophoblast cells, allowing them to proliferate before they implant into the uterine wall.

Given its multifaceted functionality, including autoimmune, neuroprotective and anti-apoptotic effects, preimplantation factor has been extensively studied as a potential therapeutic agent in both reproductive and non-reproductive medical contexts. PIF is also advantageous because of its easily replicable biochemical structure. [5] In reproductive contexts, PIF has been studied as a treatment for infertility. In women with recurrent pregnancy loss, treatment with PIF is able to rescue a non-viable embryo and promotes a successful implantation and pregnancy. [15] It does this by mitigating the toxic influence of certain factors that naturally occur in the uterus, such as acidity. [15]

PIF has also been studied in a range of other non-reproductive contexts. Due to the ability of PIF to attenuate the attack mechanisms of mononuclear immune cells, it has been implicated as a successful treatment for autoimmune diseases including diabetes mellitus type 1 in mice studies. Diabetes mellitus type 1 is characterised by the misrecognition of pancreatic beta islet cells as foreign material. [7] These studies show that PIF is able to preserve the pancreatic beta islet cell's integrity, rescuing them from the autoimmune attacks which cause diabetes. [7] In adult models, PIF also reverses the pathological neuroinflammation caused by autoimmune diseases such as multiple sclerosis. [16] It also reverses paralysis and promotes growth of neurons in patients with neurodegeneration. [10]


Embryo Implantation After IVF

What is involved in embryo implantation?

  • Successful implantation requires a competent blastocyst embryo interacting with a receptive endometrial (uterine) lining

When does blastocyst implantation actually occur after an IVF cycle – or in a normal menstrual cycle?

  • Implantation occurs on day 6-10 after the egg retrieval
  • Which is 1 to 5 days after a blastocyst transfer
  • Which is equivalent to day 20-24 of a natural menstrual cycle (idealized 28 day cycle)

How long does embryo implantation take?

  • Once the blastocyst has hatched out of its shell, the actual attachment and invasion of embryonic cells begins within one day.

What is the latest chance for implantation of an embryo after an IVF transfer?

IVF Success Rates Chicago
Our success vs. national average
Data from 2016 SART report

What percent of IVF embryos will implant?

The rate of embryo implantation varies according to multiple factors including the quality of the IVF program and female age. The graph below shows national average implantation rates from the 2012 CDC IVF report from the US government.

Implantation rate is defined as the percentage of embryos that were transferred that develop at least to the stage of fetal heart activity documented by pregnancy ultrasound.

  • Implantation rates decline with female age – mainly because of the increased rate of chromosomal abnormalities in eggs from older women
  • IVF with chromosomal screening of the embryos – PGT-A – prior to transfer is sometimes used to help overcome the “aging egg” problem


Implantation rate by age – 2010 national IVF data from the CDC
The rate of embryo implantation decreases significantly with increasing female age

Is there such a thing as “late implantation” after IVF?

There seems to be some variation in the timing of implantation, based on blood levels of the pregnancy hormone (hCG) and variations in ultrasound development at 4 to 6 weeks of pregnancy.

However, in humans there is not much leeway for late implantation because the “window of implantation” closes.

What is the cause of late implantation of an embryo in humans?

We don’t know much about this. It could be due to slower than average embryo development or late development of uterine receptivity – or a combination of factors.

How can we improve implantation rates with IVF?

IVF failure seems to be due to issues with embryo quality and not uterine issues in the large majority of cases. Part of the evidence for this comes from egg donation success rates that are excellent – even in couples that have failed IVF repeatedly using their own eggs.
Do hormones affect implantation?

In order to be receptive, the uterine lining needs to be exposed to the ovarian steroid hormones estrogen and progesterone in sufficient amounts and with proper timing.

Embryo implantation in humans

After fertilization the human embryo begins a 4 day long journey down the fallopian tube and into the uterus.

When the embryo reaches the blastocyst stage it develops two distinct populations of cells. The outer cell mass, called the trophectoderm, and the inner cell mass. There is also a fluid filled cavity – as seen in the picture below.

Components of a blastocyst embryo
Picture of a human blastocyst Inner cell mass – ICM Trophectoderm – TE More blastocyst pictures and grading issues

  • The trophectoderm component will give rise to the placenta
  • The inner cell mass will become the fetus

A healthy blastocyst embryo will continue to expand and the trophectoderm then begins to hatch out of the embryo’s shell. Hatching usually occurs on day 6 in humans. See the picture below.


Hatching human blastocyst
Hatching blastocyst embryo The shell of the embryo (zona pellucida) is at the lower left

Details about blastocyst implantation

The trophectoderm cells develop the ability to attach to the endometrial lining of the uterus. At the same time, the uterine lining develops the ability to allow invasion of the trophectoderm cells from the blastocyst.

The process of embryo implantation is described as having three phases:

Apposition is “unstable adhesion” of the blastocysts to the surface of the uterine lining.

The attachment phase involves “stable adhesion”. This phase is believed to involve signaling back and forth between the embryo and the lining.

The penetration phase involves invasion of the trophectoderm cells from the embryo through the surface of the lining deeper into the stroma of the uterine lining. In this way, a vascular connection to the mother is formed.

Timing of embryo implantation in humans

A good study of implantation was published in 1992 by Bergh & Navot. They studied 33 pregnancies from egg donation or frozen-thawed cycles (FET) with serial blood HCG levels on the mothers to find the time of the “first embryonic signal”. The HCG assay used could detect very low levels of HCG – the pregnancy hormone.

  • Average first detection of HCG was at an embryonic age of 7.1 days
  • The range of first detection was 6.6 to 7.4 days

Human blastocysts should hatch from the shell and begin to implant 1-2 days after day 5 IVF blastocyst transfer. In a natural situation (not IVF), the blastocyst should hatch and implant at the same time – about 6 to 10 days after ovulation.

What is the “window” of implantation?

After sufficient estrogen hormone exposure, initiation of progesterone hormone starts a “clock” – and the uterine lining passes through a receptive “window” of time when implantation can occur. Before, or after this window – implantation can not occur.

Rosenwaks et al, in 1987 published a study looking at donor embryo transfers done in natural cycles. They got good results when transferring 4-6 cell embryos with day 17-19 endometrium (the day of the LH surge was called day 14).

Formigli et al, in 1987 reported uterine lavage of embryos from uteri of donors at 5 days post-ovulation. The embryos were then transferred to recipient women. They had pregnancies when the recipient’s cycle was from 4 days in front of to 3 days behind the donor’s uterus at ovulation. This suggests a window of implantation of up to 7 days.

Navot et al, in 1991 reported on donor embryo transfers done with 2-3 day old embryos on recipient “cycle days” 15-20 (artificial cycles controlled with meds). Pregnancies resulted from transfers on all days. This suggests a window of at least 6 days.

The inferred window of implantation may extend from day 18 to day 24 of an idealized cycle.

Implantation in some other mammals

There are some very interesting variations among different mammalian species.

  • “Delayed implantation”, also called embryonic diapause has been described in about 100 species of mammals

Ovulation – mating – fertilization – and subsequent development to the blastocyst stage occurs. The blastocyst then remains in the uterus without implanting or developing further.

In some species, the corpus luteum cyst in the ovary is later reactivated – at which time the embryo implants and continues development.

The swamp wallaby, a marsupial, is a good example:

  • This animal mates during pregnancy, about 4-6 days before giving birth
  • The sperm enter the non-pregnant uterus (this animal has a double uterus), and the egg is fertilized
  • The resulting embryo develops to the blastocyst stage and then goes into “diapause” (like hibernation)
  • The mother gives birth to the pregnancy that was near the end, and, after the young are finished suckling, the blastocyst in diapause (in the other uterus) “wakes-up” and implants, develops, etc.

Information provided by and last updated on (6/12/2019) by: Mohamad Irani, MD

Dr. Mohamad Irani is a reproductive endocrinologist and infertility specialist.


What does implantation feel like?

There are a lot of misconceptions around whether or not someone can actually feel implantation, so let’s set the record straight.

For most people, implantation feels like nothing and some report feeling a few symptoms. “[Implantation] can lead to cramping, spotting and abdominal pain,” Dr. Langdon tells us, but some people may not notice any symptoms of implantation at all. Do you best to stay cool, calm and collected during that two-week wait—just because you’re not feeling any implantation symptoms doesn’t mean it’s not happening.


FAQs from users

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

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?

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?

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?

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.


When to See a Doctor if you Have Signs of Implantation or Pregnancy

Light spotting, mild cramping, and changes in your breasts are normal signs and symptoms of implantation and early pregnancy. However, if you think that you might be pregnant and a pregnancy home test has confirmed this, you should visit your doctor.

The American Pregnancy Association recommends visiting your healthcare provider around 8 weeks after your last menstrual period. This will help you arrange the proper prenatal care and discuss pregnancy in general and birth options. 13


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