Development of embryos in the uterus after transfer: what determines the result?

In the IVF protocol, with prolonged cultivation and no natural exit from the casing, auxiliary hatching may be recommended

How embryos behave after transfer

The presence of "breakdowns" in the genetic material can cause the death of the zygote - (the stage of development of the embryo) - by days - this is the third day after fertilization (the second day of cultivation, since the first day is considered to be zero). Until this time, development occurs by inertia - "on the mother's reserves" of the egg. On the 3-4th day, its own genome is included in the work.

The death of the embryo and a stop in the division of blastomeres - a block of development - most often occurs at this stage, but it also happens later - after the transfer, and depends on:

• formed genome;
• the success of switching development processes from "maternal reserves" to their own genetic material;
• the timeliness of such a switch;
• duration of cultivation.

The media used, even the best and most expensive ones, are not the mother's organism. Long-term cultivation is good, but not in all cases. Doctors are constantly faced with a dilemma: in the first days of development, it is difficult, and prolonged cultivation can cause a stop in development.

Therefore, they always carefully consider each individual case, and then decide on the timing of "growing in an incubator". The number of embryos obtained, the history of previous attempts and the need for (PGD) are taken into account. This study can be carried out starting from the fourth day of development. Before this period, it is technically difficult to separate the blastomere for examination.

A poor-quality genome and cultivation in environments are not all the reasons for the death of embryos, but at the initial stages of development they come to the fore. There are still problems with quality and implantability. Embryo development after transfer in the early stages - the process is delicate, multifaceted and not fully studied, since it is very difficult to find material for study. Research is ongoing in this direction to this day.

Much of a woman's knowledge of how pregnancy begins ends with ovulation and fertilization. Actually, the success or failure of the planning cycle is attributed to the fateful "meeting" of male and female germ cells. However, in the development of a new life in a woman's body there is another difficult and important point - embryo implantation... In order to increase the personal literacy of planning ladies, this issue should be given special attention.

A bit of theory

Implementation fetal egg into the uterus called implantation. The villi of the embryo invade the lining of the uterus, which can cause minor bleeding.

In order for the implantation to be successful, several conditions must be met at once:

• lush three-layered endometrium with a high content of substances that feed the embryo;
• a high amount of progesterone in the body (so that the embryo can develop and menstruation does not start);
• normal microflora in the body.

The process of fertilization and development of the ovum - not instantaneous. And each of its stages is important for the onset of a normal pregnancy and the formation of a healthy fetus.

Dates of implantation

After ovulation and the meeting of the egg with the sperm, the fertilized zygote begins to move along the fallopian tubes. Its task is to get into the uterus as quickly as possible in order to gain a foothold in the endometrium specially prepared for this. On the way, the zygote is continuously dividing and growing. In stage blastocyte implantation and happens.

We can conditionally distinguish between middle, late and early implantation.

• Early. It is quite rare. Usually, such implantation is considered early, which occurred 6-7 days after ovulation (or 3 DPP - 4 DPP when it comes to IVF)
• Average. 7-10 days pass between fertilization and implantation ( embryo implantation after transfer comes on about 4-5 days). Doctors say that the introduction of morula takes about 40 hours, after which the body begins to produce the hCG hormone into the blood, increases basal temperature... Based on this, the so-called. the embryonic period of development, which lasts until about 8 weeks of gestation.
• Late. Comes about 10 days after fertilization. This is what always gives women, at least weak, but hope for a possible pregnancy - even when there is practically no expectation.

If pregnancy does not occur for a long time, then you need to be examined to identify the cause of infertility.

Subjective and objective signs

Both in the natural and in the artificial cycle, women are very excited and want to quickly open the veil of secrecy - is there a pregnancy or not? They start collecting symptoms and sensations, trying to find in their state of health some kind of connection with reality. Experts took as a basis a simple classification, according to which all signs can be divided into subjective and objective.

Subjective:

• pulls the stomach;
• discharge;
• changes in mood, emotional lability;
• tingling in the uterus after ovulation;
• feeling tired, etc.

Girls may even point out that after IVF stomach ache like before menstruation... In this case, while there is no clear certainty, such pain may indicate both the onset of pregnancy due to successful implantation, and the approach of the end of the cycle - and the beginning of a new one.

Objective:

• the basal temperature rises after the transfer (after a slight depression in the natural cycle);
• body temperature after transfer can also rise from 37 to 37.9 degrees;
• detection of the hCG hormone in urine and blood.

In this case, one should distinguish between the levels of pain, the abundance and saturation of the discharge, the increase in body temperature. Sometimes what is passed off as ovum implantation signsis a symptom of some other disease. When in doubt whether your sensations 5 dpo signs fetal implantation or not, it's best to see a doctor.

Embryo development by day after IVF

If everything is more or less clear with the natural cycle, then the question is, on what day does embryo implantation take place in a successful protocol remains open. We bring to your attention a tablet by day:

0 DPP - transfer ( cryotransfer)

1DPP - the blastocyte leaves the membrane

2DPP - attachment of blastocytes to the uterine wall

3DPP - implantation begins

4DPP - implantation of morula into the uterus continues

5DPP - end of implantation

6DPP - the placenta begins to produce hCG

7DPP - active growth of hCG levels

8DPP - hCG continues to rise

9DPP-10 DPP - hCG levels reach the minimum of pregnancy tests

At about 11 day (11-12 DPP) after the transfer, one can draw conclusions about whether there was successful IVF.

We trust nature

Women re-read tons of literature, trying to find the very 5 dpo feelor 6 dpp sensations, which would indicate implantation and, accordingly, the onset of pregnancy. Actually, to worry about whether it worked out or not, expectant mothers begin to 3 DPO.

This question equally worries girls who have undergone the IVF procedure. The estimated embryo implantation after IVF try to catch on the minimum changes in the body and well-being. The Internet is replete with requests like “ 5 dpp three days», « 4 dpp five days ", « 7 dpp five days”, With which women seek positive stories.

A bitter disappointment is the absence of even a hint of a second page on Day 8 or menstruation after embryo transfer... But in fact, the answer to the question of whether why the embryo does not take root, there may be an objective situation of natural selection. The unviable fetus was rejected, giving way to healthy offspring.

In fairness, it should be noted that if such rejection is repeated constantly, then this is a reason for a full medical examination. The reason for the non-onset of the long-awaited pregnancy may be male infertility.

Implantation is a critical point, because the blastocyte is perceived by the woman's body as a foreign object, due to the presence of the man's genes in the cell. The speedy and successful introduction into the endometrium and the onset of a normal healthy pregnancy depend on how well the defense mechanisms of this cell work.

They say that the most powerful adrenaline rush is not a roller coaster, but waiting for the result of a pregnancy test. This is especially true for a patient after IVF. The embryo is transferred. Much has already been passed, a lot of effort, time, money has been spent. There are two weeks of endless waiting ahead….
What happens during this period? The body has already gone through a lot. Prescribed drugs (primarily progesterone and its derivatives) are designed to create optimal conditions for pregnancy. There are no other, more effective drugs for this stage yet. It remains to be patient and wait.

At this time, mild cramping pains, scanty spotting or even light bleeding, slight bloating, general fatigue and chest soreness may bother you. Symptoms shouldn't get worse. Their presence (as well as their absence) does not mean that pregnancy has not occurred.

Please note that if, after completing the IVF program, there is excessive, increasing bloating and soreness in the abdomen, shortness of breath, chest pain, or impaired urination, you should urgently contact your clinical team, as these are the first signs of hyperstimulation syndrome and intensive therapy is likely to be required.

But even if all is well, painful doubts, premonitions do not leave:

Please tell me, the absence of discharge or any other symptoms, does it indicate that the implantation did not take place again? Today I have 3DPP for two five days, according to the terms it should already happen. The first 2 days my lower abdomen ached, today I feel like an astronaut. I am very worried that there are NO sensations AT ALL …….

Help with advice: transfer of 3 good quality blastocysts. here is my HCG 5DPP - 2.8 (I already decided that the flight and all appointments were performed mechanically), 12DPP - 118.8 (I was very surprised), 14DPP 253.1. I do not fit into the table of norms of hCG. what can be done to stretch the baby? This is the 8th transfer.

Please tell me if on 7 DPP a three-day hCG is negative, is it possible to hope for a pregnancy?

Questions like this are common. In this connection, I would like to talk a little more about the early diagnosis of pregnancy, how hCG grows, and whether it is worth making any predictions based only on its values. Are laboratory studies of hormone levels and indicators of the blood coagulation system justified at this stage?

I'll start with the main thing: HCG (human chorionic gonadotropin) - a special hormone of pregnancy. It is an important indicator of the development of pregnancy and its deviations. Chorionic gonadotropin is produced by the cells of the embryonic membrane immediately after it is attached to the wall of the uterus (implantation). Based on the figure obtained, the doctor determines the presence of fetal tissue in the body, and therefore the onset of pregnancy in a woman.

The level of hCG blood can be determined as early as 6-8 days after implantation, which suggests pregnancy (the concentration of hCG in the urine depends on the sensitivity of the test and usually reaches the diagnostic level 1 to 2 days later than in the serum) It is worth noting that the timing of the appearance of the first positive hCG values \u200b\u200band the rate of its increase are similar, but in 15% of cases they do not fit into generally accepted norms and require more careful observation to make the correct diagnosis.

In 85% of cases normal pregnancy between 2 - 5 weeks, accompanied by a doubling of hCG every 72 hours... The peak concentration of hCG falls on 10-11 weeks of pregnancy, then its concentration begins to slowly fall. This is the result of the work of the "embryo-placenta" complex, it is the placenta that begins to independently maintain the necessary hormonal background. The body does not need a high content of hCG by this time.

Increased levels of human chorionic gonadotropin during pregnancy can occur with:
normal uterine pregnancy (individual characteristics in 10-15%)

• multiple pregnancy
• toxicosis
• maternal diabetes
• some genetic pathologies fetus
• trophoblastic disease
• incorrectly set gestational age
• taking synthetic progestogens (drugs from the progesterone group)

Its increased values \u200b\u200bcan also be seen within 7-10 days after an interrupted pregnancy (medical or spontaneous abortion). But the concentration of the hCG indicator in dynamics in these cases does not increase, but more often falls.

Low chorionic gonadotropin levels may indicate an incorrect setting of the gestational age or be a sign of serious disorders, such as:

• ectopic pregnancy
• undeveloped pregnancy
• delayed fetal development
• the threat of spontaneous abortion
• some other more rare conditions.

It is important to understand that a decrease in the value of hCG in repeated studies says only one thing: the development of the ovum has already stopped, it is impossible to reanimate it. An exception is a laboratory error (not often, but it happens).

Optimal terms for determining the level of hCG 12-14 days after the transfer (lower probability of error). If a two-week wait is insurmountable for you, you can donate blood earlier, starting from 7-8 days, but after receiving any (positive or negative) value of the conclusions, do not draw until you repeat the analysis 2-3 times in dynamics.

The values \u200b\u200bof hCG depending on the duration of pregnancy are in many laboratory tables, I will not repeat them here. But it is important to consider the following:

• From 0 to 10.0 mIU / ml 13-14 days after transfer - no pregnancy.
• From 10.0 to 25.0 mIU / ml doubtful value, which requires repetition, the presence of implantation is debatable.
• From 25.0 mMEml and above, a positive value, an indicator of implantation.
• When examining on the 16th day after the puncture, the level of hCG in the blood is higher than 100 mMU / ml (for embryos of 3 days) or 130 mMU / ml (for embryos of 5 days) indicates high chances of successful pregnancy, while while at lower values, the likelihood of uterine progressive pregnancy is not high.
• Any positive hCG digit dictates the need keep previously assigned support, first of all, progesterone preparations (kryynon, progesterone, urozhestan, duphaston and others). In controversial cases (the figure is below the average, there is spotting from the genital tract, etc.), it is necessary to plan repeated hCG determinations every 4-5 days. With an increase in the value of hCG, one can unequivocally talk about a progressive pregnancy, but an ectopic pregnancy cannot be ruled out.
• With a progressive decrease in hCG levels, maintaining maintenance therapy is not worth it. This will only increase the time of uncertainty and vain hopes. The most common causes of missed pregnancies are genetic disorders of the fetus. As a rule, it is not possible to maintain a pregnancy with severe genetic abnormalities. Is it worth it? Discussion of supportive therapy should be discussed with your gynecologist.
• More specific information about the onset of pregnancy can only be given by Ultrasound of the pelvic organs, which can be planned no earlier than 20-22 days after the transfer.
• The dynamics of the increase in hCG can be assessed only when lack of hCG-containing drugs in support (rotten, chorionic gonadotropin, choragon and others). A trace concentration of externally administered hCG lasts from 5 to 15 days. depending on the dose received and the individual characteristics of the organism. A sufficient number of studies have been published that indicate that the prescription of these drugs does not affect the prognosis, but significantly complicates the assessment of the results obtained.
• The level of hCG after 5 days of embryo transfer is often slightly higher than after 3 days of transfer, and practically does not depend on whether the transfer was fresh or cryo.

Another "fashionable theme" - control of blood hormone levels in the period after the transfer in order to correct support drugs.

I want to get advice, I have 18dpp, hgch 970, support: dyufaston 2tab 3 times a day, divigel 2g. Folio, passed estradiol - 725, progesterone - 15.6 ... Tell me if there is sufficient support? And are hormones normal?

***

Help me understand, 3 DPP of blastocysts, today I passed progesterone 105.0 nmol / l (1 trim: 29.6 - 106), estradiol 68 pmol / l. Injest support 2.5.% 2 p. per day, kryynon at night, proginova 0.5 tablets per day. Is estradiol low? Perhaps you need to increase progynous support?

The initial idea looked logical: you determine the level of hormones (progesterone and estrogens) in the blood and, knowing their norms, you adjust the medication prescriptions, like on a scale, adding a deficiency. These guidelines have existed in many guidelines for a while. But in practice, everything turned out to be much more complicated.

First, laboratory values \u200b\u200bof hormone levels during repeated studies in a blood vessel and in uterine vessels (obtained during surgery) were different. The concentration of hormones in the uterine tissue was much higher.

Secondly, the production of hormones is pulsating. One secretory impulse takes 60 to 90 minutes. Do not take the analysis multiple times during the day to calculate the average concentrations?

Thirdly, the level of hormones is additionally supported by the vaginal forms of gestagens, which have a slightly different chemical formula than the progesterone we know. That is, they are in the blood, but they are not determined in the analysis (another formula).
Consequently, laboratory testing of progesterone levels is of limited clinical value because does not reflect his true concentration in uterine vessels and n e is a reason to change support... It is impossible, looking at the calm water surface near the coast, to estimate the speed of the river flow in the fairway.

In the later stages of pregnancy, when the “fetus-placenta” complex is included in the work, the concentration of progesterone may be one of the indirect signs of the progression of uterine pregnancy. But by this time, more reliable information can be obtained already during ultrasound.

Determining estrogens to assess the chances of pregnancy is even less promising. A high concentration of estrogens in the blood indicates only the severity of the hyperstimulation syndrome. Correlation between estrogen value and pregnancy rate has not been shown. In addition, the introduction of estrogens from the outside in the period after the transfer is far from always justified.

I will write a little more about the myth of “ thick blood«:

I had a transfer of 2 five-day blastocysts. On the third day after the transfer, I passed D dimer, the result was 2121.6 ng / ml !!! And on the fourth I passed the RFMK, the result is 12 mg / dl (the norm is 0.00-4.00). Kolya fraksiparin 0.3 2 times a day and I take thromboass 100 mg. Please tell me, is it possible to indirectly assume that the implantation has taken place by such indicators? And why are such high rates dangerous?

Please tell me how often you need to monitor the D dimer after the transfer? And in general, is it advisable to do this? For some reason, doctors have an ambiguous opinion about high rates ... Some say that this is normal ... Others say that the therapy needs to be changed urgently, that it is very dangerous ...

The opinions of doctors in assessing this factor are really not unambiguous. In different clinics, one can hear directly opposite recommendations on the significance of altered hemostasis indices in the ART protocol. This introduces confusion, misunderstanding, who is right, is it important to "monitor hemostasis" after the transfer? Does the appointment of low molecular weight fraxiparines affect the final result?

There are always controversial topics in science. This is one of them. I am close to the position about the absence of influence of fluctuations of some values \u200b\u200bof the coagulation system on the onset of pregnancy. An increase in a number of indicators of the hemostasis system is a kind of "patches" for the repair of blood vessels, protection from obstetric bleeding.

Studies show that the incidence of thrombophilia among women requiring IVF is the same as among completely healthy women - about 7%. During IVF in women with thrombophilia, the birth rate was the same (60.8% after 6 cycles) as in women without thrombophilia (56.8% after 6 cycles) - this means that the analysis for thrombophilia before IVF is not informative, detection and treatment of thrombophilia with IVF does not affect the prognosis. In addition, many external factors can contribute to "hemostasis disorders": stimulation of ovulation, follicle puncture, the onset of multiple pregnancies and much more. Today, there are no absolute norms for coagulogram indicators for different conditions (except for assessing baseline indicators outside of stimulation and pregnancy). In this connection, I am sure that “monitoring of hemostasis” and the appointment of expensive fraxiparines, most likely, are of only commercial interest.

I'll tell you my story in a nutshell.

My husband and I were unable to get pregnant. Then there was an independent pregnancy, which ended in a frozen pregnancy at a period of 7-8 weeks. After that, they began to carefully examine and it turned out that my husband had 100% of sperm with pathology. With this they don't even take on eco. Treatment was prescribed.

Unfortunately, it turned out to be unsuccessful. I was very upset, but it was reassuring that 2 embryos remained for cryofreezing. True, their quality was not very good, to put it mildly - 4ВВ and 3ВС. Well, what to do, do not throw them away, they are still my cells and all the options must be tried.

Then the next cycle after a failed IVF I get pregnant on my own. It was a shock for me and my husband and my reproductive specialist. We were all delighted, but at 7-8 weeks, pregnancy stops developing. I had hysterics and long depression. I was really tired of all this, procedures, cleansing, pills, tests, etc. ... morally it was very difficult. It took me a long time to recover. While I was recovering, we even tried to do artificial insemination. There is a chance of becoming a parent, but it was unsuccessful.

And to be honest, I was not going to carry my snowflakes. I was afraid the pregnancy would end again. Therefore, I did not even begin to pay and extend the cryopreservation period at the Kulakov Scientific Center when my time was up.

So a year passed. And one day they called me from the center and asked if I was going to transfer my embryos? And I asked if they still exist? And I was told that without my consent they have no right to do anything with them. I was very surprised. And I decided that this is a sign and we must act.

I went to my fertility specialist, told everything. She used to work in Kulakova, did eco Do not be afraid! This is such a chance to become a mother! And now he works elsewhere. My doctor called the doctor in Kulakov, who took me there, and said that we want to do cryo. She gave the go-ahead. From the 4th day of the cycle, we entered the cryoprotocol My successful cryoprotocol experience at the Kulakov Scientific Center. He was already fully paid and did not go through the OMS. All together it came out about 30,000 rubles.

I was prescribed medications:

43 Proginova 1 t 2 times a day Well builds up the endometrium. I took it with cryoprotocol on HRT.

Divigel 1g

every day I went to Kulakov for an ultrasound scan and monitored the growth of the endometrium.

15 were appointed to transfer 2 embryos. They defrosted successfully. They were transferred, shown on ultrasound, how they were located in the uterus. From support, they also left Proginova, Divigel and added a horse dose of 800 Utrozhestan per day (4 tablets).

From sensations at all, nothing, even the chest is not swollen and does not hurt.

1 dpp. The next day I went to work. There are no sensations at all.

2 dpp no \u200b\u200bsensations

3 DPP began to pull the stomach as before menstruation. I was upset, I decided that it was a flight.

4 dpp no \u200b\u200bsensations, the stomach is gone. The chest is silent.

5, 6, 7 dpp no \u200b\u200bsensations

8 dpp I could not stand it and did the test and it is POSITIVE! The second bold line appeared immediately.

On 9th DPP I went to Invitro to take HCG and it turned out to be 337. Huge! Maybe there are twins?

I called and made my doctors happy. One of them immediately put me on sick leave. I sat on it all the first trimester.

On the first ultrasound, it turned out that there is one embryo in the uterus.

I gave birth to him in my native NTs Kulakov. My birth in the new federal perinatal center in the NTs im. Kulakova OCTOBER 2016

Summing up, I want to say that the cryoprotocol is much easier to transfer than a fresh one, because it does not require stimulation and puncture.

Pregnancy is no different from natural pregnancy, only the support itself was finally canceled at 30 weeks.

Girls, for inspiration, I'll describe the symptoms in my successful (pah-pah-pah) protocol.

They planted two five-day days. Interestingly, this time everyone got up and walked from the chair. Sami, yeah, imagine. No one was taken to the ward on a gurney. And in general they did not give a second to lie down. After replanting, the girls immediately went down to see a doctor. And everyone was advised to have a good sex life on the day of transfer. For blood circulation. Yes, yes, I was also in shock.

I walked from the clinic to the house - the sun was shining, the weather was good - let me, I think, take a walk, since such chaos is happening in the kingdom. Then I read: all this is completely normal - nothing can fall out of the uterus if the cervix is \u200b\u200bclosed. Moreover, when we are in an upright state, it lies horizontally and the embryos from there will not go anywhere at all.

The temperature rose by 1DPP, stayed at 37 for two days. I constantly wanted to sleep, I was ready to sleep standing anywhere. A metallic taste appeared in my mouth. The chest has grown dramatically (but this is not a symptom against the background of progesterone). I started running to the toilet all the time.

My stomach pulled a little and still sips (not much, I don't even drink Noshpu, although ten minutes ago such an idea flashed through).

The sleepy state continues to this day. I go to the store for food (I haven't cooked for a week, I have no strength, I can hardly drag my legs) - and I'm already tired, I need to sleep for an hour.

I passed hCG on 8DPP, the poet's soul could not bear it. Showed 281. Most likely, both babies were attached !!! Now I am waiting on March 9 to submit the official analysis.

Of course, this is all nature, chance, etc. Still, I believe that a positive attitude helped. There are many studies showing that women who are positively minded and believe in the result are more likely to become pregnant during IVF. Before the implantation, I purposefully worked with my fears (fear of pregnancy, fear of losing my job, and I'm also the most unlucky in the world, etc.). I reformulated them into positive attitudes and repeated it to myself ten times every day. I got this attitude: “Getting pregnant is easy and natural. The world loves me and cares about my comfort and well-being. I can bear, give birth and raise healthy children. Nature is wise and she will help me in this. "

I also listened to Sinelnikova's meditation for pregnant women (she is in social networks, look for whoever needs it), fell asleep under it during the day. I drew a visualization picture - a child in a tummy (I had not even dreamed of two yet) and now my husband and I are walking on the street - I put it in a frame, hung it on the wall. As I pass by, I will definitely admire.

Of course, I can only rejoice quietly, there are still many stages to go through. But the first result is already there. Here it is, the coveted file in the mail (god, is this really happening to me).