What Causes Recurrent In Vitro Fertilization Failure?
In in vitro fertilization treatment, it is not possible for every embryo transfer to result in pregnancy. However, if pregnancy cannot be achieved despite the transfer of well-developed embryos more than once, the reasons for the failure can be evaluated in more detail. This situation occurs in daily userecurrent in vitro fertilization failureAlthough it can be called as, the concept of recurrent implantation failure is also used medically to prevent pregnancy despite embryo transfer.
0stanbul recurrent in vitro fertilization success 1In its evaluation, it is not enough to look only at the last treatment. The woman's age and ovarian reserve, the development of the obtained eggs and embryos, sperm characteristics, uterine internal structure, endometrium, technical details of previous transfers and drug protocols used should be examined together. Assoc. Dr. The purpose of the evaluation to be performed by Nazlı Korkmaz is not to request unnecessary tests, but to determine whether there is indeed an addable factor in the previous tests.
What is Recurrent IVF Failure?
Failure of in vitro fertilization treatment may occur at different stages. In some patients, sufficient eggs cannot be obtained, some eggs may not be fertilized, some embryos may not reach the blastocyst stage, or the transferred embryo may not be able to attach to the uterus. For this reason, “in vitro fertilization failure” and “implantation failure” are not the same situation.
There is no single transfer number valid for everyone for recurrent implantation failure. A more accurate approach is to make a personalized evaluation, taking into account the age of the patient, the developmental characteristics of the transferred embryos, whether the embryos have been genetically evaluated, and the possibility of pregnancy expected in each transfer.
Article summary
There is no single reason for recurrent in vitro fertilization failure. Chromosomal structure and development of the embryo, female age, intrauterine problems, endometriosis or adenomyosis, hydrosalpinx, hormonal preparation and factors related to embryo transfer are the main areas that need to be evaluated.
What Will You Find in This Article?
- What is Recurrent IVF Failure?:The difference between a failed IVF cycle and implantation failure is explained.
- Why Repeats?:Embryo, uterus, tubes, endometrium, genetics and possible transfer-related factors are discussed.
- What Tests Are Performed?:Evaluation options, from reviewing previous treatment records to ultrasound and hysteroscopy, are explained.
- How to Plan the Next IVF Trial?:A personalized treatment approach is explained according to the identified cause.
Is Every Failed In Vitro Fertilization Trial a Failure of Implantation?
No. If the egg does not develop during the treatment, the egg cannot be collected, fertilization does not occur, or the embryo does not reach the transfer stage, this is not considered as implantation failure. In order to talk about implantation failure, embryo transfer into the uterus must be performed.
This distinction is important for planning subsequent treatment. For example, in a patient whose ovaries respond inadequately to medications, the evaluation focuses on ovarian reserve and stimulation protocol, while in a patient in whom pregnancy does not occur despite repeated transfers of well-developed embryos, the embryo, intrauterine and transfer factors can be examined in more detail.
What Causes Recurrent In Vitro Fertilization Failure?
The attachment of the embryo to the uterus is a very complex process. Successful implantation requires an embryo with development potential, a suitable endometrium, and a healthy embryo-endometrium interaction at the right time.
The cause of recurrent failure may not be determined in every patient. The areas most frequently taken into consideration in the evaluation can be summarized as follows.
| Evaluated Area | Possible Factors | Evaluation |
|---|---|---|
| Embryo | Chromosomal irregularity, developmental potential and embryo quality | Previous embryology records and genetic evaluation in selected patients |
| intrauterine | Polyp, intrauterine myoma, adhesion or uterine shape anomalies | Ultrasound, sonohysterography or hysteroscopy when necessary |
| uterus and pelvis | Adenomyosis, endometriosis or hydrosalpinx | Ultrasound and additional imaging when necessary |
| Endometrium and hormones | Endometrial thickness and timing of progesterone supplementation | Re-examination of treatment protocol and transfer cycle |
| embryo transfer | Difficult transfer, uterine stenosis or technical factors | Evaluation of previous transfer records and application technique |
| Genetic | Chromosomal structural changes of the parents in selected couples | If necessary, karyotype and genetic consultancy |
Not every examination in the table is applicable to every patient.Test selection should be based on what has happened in previous trials and the patient's personal clinical characteristics.
Embryo Based In Vitro Fertilization Failed 1
The chromosomal structure of the embryo is one of the most important determinants of implantation. Even if the embryo is considered to be of good quality externally, it may not be chromosomally normal. The likelihood of chromosomal irregularities increases, especially as women get older.
For this reason, it may not be correct to look for problems only in the uterus in successive unsuccessful transfers. The number of eggs obtained in previous treatments, fertilization rate, what day the embryos reached, blastocyst development and embryo ratings should be examined together.
Why Does Female Age Affect In Vitro Fertilization Success?
As a woman's age increases, not only the egg reserve decreases, but also the possibility of chromosomal irregularities in the eggs increases. For this reason, the pregnancy probabilities of women of different ages who are transferred the same number of embryos and of similar morphological quality may not be the same.
Especially in the evaluation of recurrent failure, ignoring the age factor and associating the entire problem with the uterus or the immune system may lead to incorrect results.
“In case of recurrent in vitro fertilization failure, the aim is not to request dozens of tests; it is to accurately determine at which stage of the previous treatment the probability of success decreased.”
Is Embryo Genetic Testing (PGT-A) Necessary?
PGT-A is a method that aims to evaluate the chromosome numbers in cell samples taken from embryos that have reached the blastocyst stage. Especially in some patients who have experienced repeated unsuccessful transfers with embryos that have not been genetically evaluated before, the embryo may be interviewed to evaluate the contribution of the chromosomal structure to the process.
However, PGT-A is not a method that should be applied to every IVF patient or after every unsuccessful attempt. Whether or not to perform the test should be decided by considering the woman's age, the number of embryos available, previous treatment results, genetic history and the couple's expectations.
For more detailed information about genetic evaluation methods in embryosGenetic Screening (PGT) in In Vitro FertilizationYou can review our article.
Do Problems in the Uterus Prevent the Embryo from Adhering?
The structure of the uterine cavity where the embryo will be placed is important for implantation. Intrauterine polyps, submucous myomas extending into the uterine cavity, intrauterine adhesions and some congenital uterine anomalies are considered among the factors that may negatively affect implantation.
Even if the uterine cavity has been evaluated before, in case of recurrent failure, repeat ultrasound, sonohysterography or hysteroscopy may be considered if there is clinical necessity. However, it cannot be said that every patient with normal ultrasound findings should automatically undergo hysteroscopy.
Can Hysteroscopy Be Used in Recurrent IVF Failures?
Hysteroscopy is a method that allows direct visualization of the uterine cavity using a thin optical system. When suspicious polyps, submucous myomas, intrauterine stickiness or other cavity problems are found, it can be used for diagnosis and, if necessary, for treatment in the same session.
Assoc. Prof. in recurrent unsuccessful transfers. Dr. When planning an intrauterine evaluation by Nazlı Korkmaz, ultrasound and previous imaging results are first examined. The necessity of hysteroscopy should be decided according to clinical findings, not as a standard for all patients.
For information about the evaluation of the uterine cavity and the application areas of hysteroscopyIstanbul HysteroscopyYou can review our content.
Do Myomas and Polyps Affect the Success of IVF?
In particular, submucous myomas and some endometrial polyps that distort the shape of the uterine cavity may affect the area where the embryo will be placed. However, it cannot be said that every myoma that grows towards the outside of the uterus or does not disrupt the uterine cavity needs to be operated on before in vitro fertilization.
The size of the myoma, its relationship to the uterine cavity and its location are evaluated with ultrasound to determine whether treatment is necessary. Avoiding unnecessary surgery is especially important in patients planning pregnancy.
Can Endometriosis Cause Recurrent IVF Failure?
Endometriosis is one of the gynecological diseases associated with infertility. It can affect ovarian reserve, the anatomy within the pelvis and different stages of the reproductive process. However, not every patient with endometriosis develops implantation failure.
In patients with recurrent in vitro fertilization failure and suspected endometriosis, pain history, ovarian ultrasound, previous surgeries and previous in vitro fertilization results should be evaluated together. Treatment is determined not only by the presence of endometriosis, but also by the patient's age and pregnancy plan.
For detailed information about the symptoms of endometriosis and its effects on pregnancyWhat is Endometriosis (!chocolate Cyst)?You can review our article.
Does Adenomyosis Affect Embryo Adhesion?
Adenomyosis is the presence of endometrium-like tissue within the muscle layer of the uterus. Some studies suggest that adenomyosis may negatively affect implantation and pregnancy outcomes. This situation can be taken into account in the treatment plan, especially in patients with significant adenomyosis detected by ultrasound or MRI and experiencing recurrent failure.
However, there is not enough evidence to support the application of the same drug or surgical treatment to every patient with adenomyosis before in vitro fertilization. An individualized decision should be made taking into account the prevalence of the disease, symptoms and previous treatments.
Can Hydrosalpinx Cause In Vitro Fertilization Failure?
Hydrosalpinx is a condition in which the fallopian tube bleeds and accumulates fluid in it. If the fluid in the tube reaches the uterine cavity, it may have a negative effect on the endometrium and embryo implantation. For this reason, the presence of a significant hydrosalpinx is important before in vitro fertilization.
If hydrosalpinx is detected in evaluations such as ultrasound or uterine film, it is evaluated individually whether surgery or different treatment options are required before transfer.
Does Endometrium Thickness Affect the Success of In Vitro Fertilization?
Endometrium is the tissue in which the embryo settles in the uterus. Before transfer, the ultrasound appearance and thickness of the endometrium are evaluated. Recurrent thin endometrium development in some patients may be a factor that may affect the possibility of pregnancy.
However, it cannot be said with certainty that the transfer will be successful or unsuccessful by looking at a single millimeter. The development of the endometrium, hormonal preparation, previous transfer results and the person's clinical condition should be evaluated together.
Are Progesterone and Embryo Transfer Timing important?
Progesterone hormone plays a fundamental role in making the endometrium suitable for the implantation of the embryo. The relationship between progesterone start time and transfer day is important, especially in frozen embryo transfers prepared with medication.
In case of recurrent failure, it is possible to re-examine previous treatment protocols in terms of progesterone type, dose and timing. However, there is no single and definitive progesterone protocol that should be applied to all recurrent failure patients.
Can Difficult Embryo Transfer Affect Success?
Embryo transfer is a short but important stage of in vitro fertilization treatment. Difficulty passing the catheter into the uterus, stenosis in the cervix, or requiring excessive manipulation during transfer may affect the likelihood of success in some patients.
If there is a history of difficult transfer in the previous transfer notes, the uterine lining and transfer plan can be re-evaluated before the next attempt. Appropriate and as atraumatic transfer as possible is aimed under ultrasound guidance.
Can Chronic Endometritis Cause Recurrent Failure?
Chronic endometritis is long-term inflammation in the inner layer of the uterus. Chronic endometritis may be investigated in some cases of recurrent implantation failure. Endometrial biopsy and special pathological evaluations can be used when deemed necessary in diagnosis.
However, since there is no complete standard regarding the diagnostic methods and threshold values used for chronic endometritis, it is not right to perform a routine biopsy on every unsuccessful in vitro fertilization patient. Examination should be planned based on clinical suspicion and previous treatment history.
Is the male factor important in recurrent IVF failure?
Since half of the embryo's genetic material comes from sperm, the male factor should not be excluded from evaluation. Previous semen analyses, fertilization rates and embryo development can be reviewed together. If necessary, sperm analysis may be repeated or an andrology evaluation may be requested.
However, there is insufficient evidence to suggest that advanced testing, such as sperm DNA fragmentation testing, should be routinely performed in all couples with recurrent implantation failure. Tests should only be preferred in cases that truly change the clinical decision.
Can Mother or Father Have Chromosome Problems?
In rare cases, there may be structural chromosomal differences, such as a balanced translocation, in one of the parents, which do not affect the health of the person but may increase the risk of chromosomal imbalance in embryos.
If there is recurrent implantation failure, pregnancy loss, or other genetically suspicious findings in the couple's history, parental karyotype and genetic counseling can be evaluated in selected patients.
Are Immune System Tests Necessary?
NK cells, various cytokine tests and different immune system panels are frequently brought to the agenda in cases of recurrent in vitro fertilization failure. However, a clinically strong and standardized relationship has not been demonstrated between the results of a significant portion of these tests and the likelihood of live birth.
Similarly, it is not right to routinely apply IVIG, intralipid or different drugs that suppress the immune system, just because "in vitro fertilization did not work a few times". Possible side effects of treatments should be taken into account as well as their benefits.
Do Blood Thinning Injections Increase Success?
Heparin and similar blood thinning drugs may be necessary in certain clotting diseases or different medical indications. However, it has not been conclusively shown that empirically administering blood thinners in every patient with recurrent implantation failure increases the live birth rate.
For this reason, medication should not be started without a clotting disorder or another medical indication. Unnecessary use may cause bleeding and other side effects.
Is the ERA Test Done for Every Repeated Failure?
Endometrial receptivity tests aim to determine a personalized transfer time by evaluating gene expressions in the inner layer of the uterus. Although early studies suggested that this approach might be useful, more recent studies have not clearly shown that routine practice increases the live birth rate.
For this reason, ERA or similar endometrial receptivity tests should not be considered among the standard tests that should be automatically applied in cases of recurrent in vitro fertilization failure.
Should Endometrial Scratching Be Done?
Endometrial scratching is one of the methods used in the past to increase implantation in subsequent embryo transfer by creating a small controlled damage to the inner layer of the uterus. However, current evidence does not show that routine application of this procedure in cases of recurrent implantation failure increases the likelihood of pregnancy or live birth.
Therefore, endometrial scratching is not a standard approach simply because previous transfers have failed.
"After repeated failure, more tests do not always mean better treatment. The important thing is to choose the studies whose results will actually change the treatment decision."
What Tests Are Performed in Recurrent In Vitro Fertilization Failures?
The first and most important stage of the evaluation is a detailed examination of previous in vitro fertilization files. Then, what investigations are necessary can be understood by evaluating these records.
- Evaluation of the woman's age and ovarian reserve,
- Examination of previous ovarian stimulation protocols,
- Evaluation of the number of eggs collected and the rate of mature eggs,
- Examining fertilization rates,
- Reviewing the developmental days and quality records of the embryos,
- Evaluation of technical details of previous embryo transfers,
- Examination of the uterus and ovaries with transvaginal ultrasound,
- Evaluation of the uterine cavity with sonohysterography or hysteroscopy, if necessary,
- Evaluation for hydrosalpinx, endometriosis or adenomyosis,
- Genetic or chronic endometritis examinations can be performed in selected patients.
0stanbul Repeated In Vitro Fertilization Success Review
Recurrent in vitro fertilization failure in IstanbulIt is important to re-analyze each previous treatment in patients presenting with this condition. Just “how many times has it been tried?” not the question; In each attempt, it should be evaluated how many eggs were collected, how many were fertilized, how many embryos reached the blastocyst, and what happened after the transfer.
Assoc. Dr. In the personalized evaluation to be performed by Nazlı Korkmaz, uterine and ovarian ultrasound, previous embryology reports, transfer records and medication protocols used are considered together. Thus, any correctable factors, if any, can be determined and a justified plan can be created instead of repeating the new treatment in the same way.
How to Treat Recurrent IVF Failures?
There is no single treatment that can be applied to everyone for recurrent in vitro fertilization failure. Treatment should be directed to the identified or strongly suspected cause. While intrauterine polyp is being treated in one patient, the ovarian stimulation protocol may be rearranged to improve embryo development in another patient.
- Personalization of the ovarian stimulation protocol,
- Re-evaluation of embryology and previous embryo development records,
- Treatment of intrauterine polyps, submucous myomas or adhesions in appropriate patients,
- If there is hydrosalpinx, treatment planning before transfer1,
- If endometriosis or adenomyosis is detected, a personalized approach is created,
- If there is a problem with the transfer technique, the next transfer should be planned accordingly,
- Genetic counseling and evaluation of appropriate genetic tests in selected patients,
- It is possible to reconsider hormonal preparation and progesterone support.
What Can Be Changed in the Next IVF Trial?
Even if it is thought that a change should be made in the next attempt, there must be a specific reason for the change. If sufficient eggs were obtained and good embryo development was observed in the previous treatment, it may not be necessary to randomly increase the drug dose. Similarly, if the uterine evaluation is normal, it may not be appropriate to perform surgery just because of a failed transfer.
The correct approach is to identify the strong and weak points of the previous treatment and make changes only in areas that may affect the result.
To learn all stages of in vitro fertilization treatment from ovarian stimulation to embryo transfer0Istanbul In Vitro Fertilization TreatmentYou can review our page.
Is Pregnancy Possible After Repeated Failure?
Yes. Having more than one failed embryo transfer does not mean that pregnancy cannot be achieved in subsequent attempts. Even in patients where no correctable problem is detected, successful pregnancy can occur in subsequent embryo transfers.
Therefore, instead of focusing only on new tests after failure, age, number of remaining embryos, ovarian reserve and the total pregnancy probability of the treatment should be evaluated together. In some patients, the best approach may be to proceed with a well-planned new embryo transfer without any additional intervention.
Frequently Asked Questions About Recurrent IVF Failures
After how many unsuccessful in vitro fertilization attempts should an investigation be conducted?
There is no fixed number1 valid for everyone. The woman's age, the number and quality of the transferred embryos, whether they have been genetically evaluated, and the expected pregnancy probability in previous transfers should be evaluated together.
Do two failed embryo transfers mean there is a serious problem?
No. Two unsuccessful transfers do not necessarily mean that there is a disease in the uterus or immune system. Many factors, including the chromosomal structure of the embryos, can cause failure. Clinical evaluation should be made individually.
Why doesn't a good quality embryo take hold?
The expression “good quality” in the embryo mostly refers to morphological features evaluated under the microscope. It cannot be said that an embryo that looks good is chromosomally normal. Additionally, intrauterine and transfer-related factors may also affect implantation.
What is the most common reason for embryo failure?
The chromosomal structure of the embryo, especially chromosomal irregularities associated with female age, are among the important reasons for implantation failure. However, the cause of failure may be different in individual patients and sometimes the exact cause may not be determined.
Is hysteroscopy necessary for recurrent failure?
No. Hysteroscopy is not a procedure that should be performed routinely on every patient. It can be applied if there is a suspicion of an intrauterine problem based on ultrasound or history or if re-evaluation of the uterine cavity is deemed clinically necessary.
Does PGT-A definitely increase the success of in vitro fertilization?
No. PGT-A may help evaluate the chromosome number of the embryo, but it has not been shown to definitively increase the likelihood of live birth in all patients with recurrent implantation failure. The decision should be made by discussing the advantages and limitations in selected patients.
Is it necessary to have an ERA test?
It has not been clearly shown that routine use of ERA and similar endometrial receptivity tests increases the live birth rate. Therefore it is not recommended to do it automatically as only a few transfers fail.
Could the immune system be rejecting the embryo?
Embryo implantation involves complex mechanisms related to the immune system. However, it is not correct to explain recurrent failure simply as "the body rejects the embryo". There is insufficient clinical evidence to support the routine use of NK cell testing and different immunological treatments.
Does the blood thinner injection help the embryo implant?
Blood thinning treatment may be required for certain medical reasons. However, since only embryo transfer fails without any coagulation disease or other indication, it is not certain whether the use of heparin increases the success.
Is sperm DNA testing necessary for recurrent failure?
Sperm factor is a part of the general infertility evaluation. However, there is insufficient evidence to support routine sperm DNA fragmentation testing in all couples with recurrent implantation failure.
Will in vitro fertilization fail if there is endometriosis?
No. Many patients with endometriosis can achieve pregnancy with in vitro fertilization treatment. The prevalence of the disease, ovarian reserve, age and other accompanying causes of infertility may affect the treatment outcome.
Can in vitro fertilization be performed again after repeated failure?
Yes. A new trial can be planned after previous treatments have been evaluated in detail. If a correctable cause is found, it is treated; If no obvious cause is found, it may be appropriate to continue with a new transfer or treatment cycle instead of unnecessary interventions.
What should be done for recurrent in vitro fertilization failure in Istanbul?
Recurrent in vitro fertilization failure in IstanbulFor this reason, when making an evaluation, if possible, embryology reports of previous treatments, hormone results, ultrasound records and embryo transfer information should be consulted. Assoc. Dr. These data can be evaluated together by Nazlı Korkmaz and a personalized next treatment plan can be created, avoiding unnecessary repeat tests.