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Implantation failure: one of the most complex reasons that makes it difficult to get pregnant

Specialization and personalization have allowed Instituto Bernabeu to become an international benchmark for the treatment of difficult cases.

Bernabeu Institute

To speak of implantation failure and recurrent miscarriage is to address the situation of many couples who struggle, without success, to obtain a pregnancy. A story with multiple chapters, which represents a lot of pain and a feeling of incomprehension for those who live it. At the same time, it represents a challenge for experts in reproductive medicine. In most of these cases, everything seems to be fine, except that the pregnancy does not occur, even after carrying out treatments ofin vitro fertilization (IVF). Sometimes, although very common, the embryo implants in the uterus, but a miscarriage occurs early, which occurs in 2-5% of cases. 

Bernabeu Institute Madridexplains that there are many factors that can cause this situation, ranging from uterine anatomical abnormalities to genetic, immunological, endocrinological factors, etc. The medical specialization and the personalization of each treatment are essential to detect the causes and to administer the best treatment to the patients.

Faced with repeated implantation failure, the specialists at Instituto Bernabeu believe that it is essential to study in depth the three parties involved in the process: the woman, the man and the embryo. This analysis starts with the study of the clinical data of the family, the analysis of their lifestyles, as well as the exposure to toxic agents, among others, which can affect the nesting of the pregnancy.


By itsImplantation Failure and Repeat Miscarriage Unit, Instituto Bernabeu carries out constant lines of research, which have given rise to particularly important genetic studies in this area. One of the most important is that which studies the identification of genetic variants that predispose to repeated embryo implantation failure and early miscarriage. This discovery led to the creation of the testIBGen RIF. This test analyzes variants in genes linked to immunological factors, associated with thrombotic risk, and factors that modulate endometrial receptivity.

Recently, research has focused on thevaginal microbiome  and on the proof that it is possible to improve the prognosis of patients thanks to its perfect balance and the normalization of the microorganism patterns of the female reproductive system.


Chromosomal alterations

Alterations in the embryo (embryonic factor) hide behind most cases ofimplantation failure and recurrent miscarriage, due to alterations in the number or arrangement of chromosomes, as reported by Instituto Bernabeu. Thanks to analyzes carried out, such as thepreimplantation genetic testing or diagnosis (PGT/PGT), it is possible to detect chromosomal alterations and therefore to avoid the implantation of an embryo that would not nest in the maternal uterus or would cause an early miscarriage. Currently, molecular biology techniques make it possible to select embryos whose chromosomes show no abnormality and which can give rise to an ongoing pregnancy. Furthermore, the study of theexome(which analyzes the regions where most genetic changes occur) represents a great advance in discovering the genetic cause of repeated miscarriages and nest failures. Once the variant has been identified, it is possible to avoid miscarriage by employing preimplantation genetic diagnosis techniques, which detect monogenic diseases (PGD-PGT-M).


Study of the uterus

The study of the uterus is also fundamental. A study by Instituto Bernabeu on the contractility of the uterus has become an international reference, since it has discovered that it is possible, thanks to a treatment that inhibits contractions, to increase the chances of nesting of the pregnancy. Possession of powerful ultrasound devices makes it possible to determine the most suitable place to carry out the embryo transfer and allows to collect all the information from the uterine cavity and to identify diseases such asadenomyosis, which complicates pregnancy, as it covers the uterus with endometrial tissue, as well as diagnoses uterine malformations that are a cause of miscarriage. Thorough monitoring of the patient, by measuring serum progesterone, is also essential for success.

To detect the reasons for which the embryo does not implant, endocrinological, hematological and immunological factors are also analyzed, since the immune system is another figure, although it is partly unknown in the reproductive process, that new research makes it occupy more and more a particular importance in this one. 


man analysis

The man also occupies an important place in the analysis of the causes involved in implantation failure and recurrent miscarriages. At present, it was revealed that a conventional spermogram was not enough to know in depth the fertility capacity. There may be altered seminal parameters that affect reproductive success. These measurements are detected by advanced studies such as thesperm meiosis, FISH on spermatozoa and DNA fragmentation. These analyzes make it possible to ascertain whether there are any alterations in the genetic load of the spermatozoa.


There is no single formula for all cases

As discussed, there are many factors in the search for causes that can cause implantation failure and/or early miscarriage. The team of medical specialists is the one that analyzes each case in a personalized way and sets the recommended examinations. Instituto Bernabeu stresses that it is particularly important not to apply general treatment formulas and to approach each case individually, since each case is unique. 


International benchmark in research

Theresearchcarried out by Instituto Bernabeu have been published in the conferences of the most important scientific societies in the world, including ASRM, ESHRE, ASEBIR and SEF. They serve, on the one hand, to be applied in clinical practice and, on the other hand, to help the scientific community in the search for solutions. The Implantation Failure and Miscarriage Unit is more specifically a European reference, in which high-level professionals and experts participate, such as gynecologists, endocrinologists, molecular biologists, geneticists, embryologists and immunologists. 

The excellent results of Institut Bernabeu and its international prestige have motivated couples from 137 countries to choose it to follow its personalized fertility treatments. Instituto Bernabeu currently hasclinics in Spain and outside, to Madrid,Alicante,Palma de Mallorca,Albacete,Cartagena,Elcheandbenidorm, as well asVenice(Italy).

Bernabeu Institute

Ovarian ageing: one of the great challenges of reproductive medicine
The Low Ovarian Reserve Unit at Instituto Bernabeu offers solutions against
egg depletion.

L'infertilityis a worldwide problem that affects millions of couples. For nearly four decades, assisted procreation has tried to offer solutions to couples who cannot have children naturally. An international reference is in Spain. The clinicBernabeu Institutestands for excellence in reproductive medicine.Our treatmentsare tailored to each patient. Since 1985, we have enabled the birth of more than 20,000 children and treated more than 125,000 patients from 137 different countries. A medicine where the patient is the center, where each person is unique, just like their treatment. The results are certified and audited by external bodies.


Instituto Bernabeu has specific treatment units that are an international benchmark, includingImplantation Failure and Repeat Miscarriage UnitandLow Ovarian Reserve Unit. Instituto Bernabeu has 8 clinics located in Alicante, Madrid, Mallorca, Albacete, Cartagena, Elche, Benidorm and Venice (Italy).

As the clinic points out, unlike in men, where fertile ability is maintained throughout adult life, in women it has an expiration date. Our body is constantly regenerating as it replaces old cells with new ones, with the exception of eggs.


"The ovarian reserve, i.e. the total number of oocytes a woman will have, is fixed before she is born and will decrease over time" as explained by Dr. Rafael Bernabeu,medical director of Instituto Bernabeu. Of the 5-6 million that her body creates during her conception in her mother's womb, this figure will be reduced to 2 million at the time of her birth and will not exceed half a million when she has her first period. At the age of 40, he will be almost exhausted. Therefore, from the age of 35, each birthday reduces the possibilities of being a mother with her own eggs, and from the age of 40 the fall is drastic. “From the age of 36, there is a loss of 2% per month of being able to have a pregnancy, or 24% less per year. This decline is all the more dizzying at a more advanced age,” as Dr. Rafael Bernabeu points out.




Having a low ovarian reserve nowadays does not in any case imply the impossibility of becoming a mother with clean eggs, but on the other hand complicates the process ofin vitro fertilization (IVF). This is one of the great challenges of reproductive medicine and Instituto Bernabeu, one of the main European leaders in infertility research, has been focusing its R&D&i projects on it for more than a decade. solutions.


Its low ovarian reserve treatment unit designs personalized treatments tailored to the specific needs of each patient. She applies, for example, pharmacogenetics, which makes it possible to adapt the hormonal treatment to the genetic profile of the ovary of each woman and thus to obtain more oocytes after the stimulation of the ovaries, by applying her testIBgen IVF. This unit, thanks to its verified research, offers certain patients double stimulation in the luteal phase after ovulation, which has been shown to increase the number of oocytes in this second consecutive cycle.




Currently, there is a promising line of action through regenerative medicine that uses biological material from the patient herself to reactivate her ovarian activity. The group from Alicante immediately applies the two “ovarian rejuvenation” techniques which have been scientifically verified. On the one hand, the activation of "sleeping" follicles by the intraovarian administration ofplatelet-rich plasma (PRP)and growth factors from the patient's blood, which facilitate the reactivation of her ovarian function.


The second strategy is ovarian activation byfragmentation and transplantation of ovarian cortex(Ovarian Fragmentation for Follicular Activation-OFFA-), to obtain an ovarian response in patients diagnosed with early menopause or premature ovarian failure.

Bernabeu Institute

activation of the ovary with platelet-rich plasma (PRP) from the patient and ovarian autograft for its regeneration

New techniques in ovarian rejuvenation can regenerate tissue to activate “sleeping” follicles, obtain more eggs and increase the success of IVF


Regenerative medicine is currently applied in various therapeutic areas. It is based on the patient's capacity for self-healing, so that her body can use its own systems, sometimes with external help, to recreate cells and rebuild tissues and organs. Although this is an experimental area, it is starting to show promising results.

Late motherhood is a reality in today's society. Ovarian failure or age is behind many cases of women with low ovarian reserve. Instituto Bernabeu is the international leader in its treatment, thanks to personalized strategies to obtain one more egg in ovarian stimulation, which can be the key to obtaining pregnancy.

In 2014, Instituto Bernabeu revolutionized the panorama of assisted reproduction by applying pharmacogenetics to cases of poor ovarian response, which thus makes it possible to apply the most suitable treatment according to the genetic profile of the ovary of each patient. A posteriori, personalized ovarian stimulation techniques were incorporated, such as luteal phase stimulation, which made it possible to optimize the response of the patient's ovary to obtain a greater number of oocytes and therefore more embryos .

New strategies are currently being developed to provide a solution to this group of patients who have residual follicles that remain inactive. Efforts are being made to investigate new techniques to "wake up" these follicles which may result in more eggs during the stimulation vitro fertilization.Although a large number of experimental procedures are being evaluated, after scientific review of the available evidence, Instituto Bernabeu has instituted those which have been shown to be safe for the patient and which show positive clinical results.



The most effective treatment for this isintraovarian administration of platelet-rich plasma (PRP)that Instituto Bernabeu is currently successfully applying to specific cases of patients with poor response and early menopause. The patient's blood, which is previously prepared in the laboratory, is then used. A “centrifugation” process is then performed, in which the platelets release a large amount of growth factors.

Instituto Bernabeu gynecologist Dr. Ana Fuentes explains that the development of follicles at particularly early stages depends on growth factors. Thus, the administration of platelet-rich plasma directly into the ovary can increase the concentration and positively affect its "awakening". The goal is to “rejuvenate” or activate the ovary by trying to get more eggs.

To treat patients diagnosed with ovarian failure or early menopause, ovarian activation is currently performed using the OFFA (Ovarian Fragmentation for Follicular Activation) technique.fragmentation and autograft of ovarian cortex. It consists in carrying out an excision of a part of the ovarian cortex of the patient, obtained after a laparoscopy. It is then split and again introduced into the ovary. The healing capacity makes it possible to activate the "sleeping" residual follicles present in patients with ovarian failure. Pregnancies, both spontaneous and after in vitro fertilization (IVF), have been published.

So far, these techniques have only shown improvement in certain patients with particular characteristics. There are a series of contraindications to take into account, such as the presence of pathology in the ovary, the existence of a single ovary or ovarian failure due to genetic causes or after chemotherapy. The medical team is therefore the one who must assess whether the treatment can be effective in the specific case.

The Instituto Bernabeu group, which has clinics in Alicante, Madrid, Majorca, Albacete, Cartagena, Elche and Benidorm, as well as a clinic abroad, in Venice, accumulates a great experience of success in the cases of patients who obtain very few oocytes after ovarian stimulation. L'low ovarian response unite is an international pioneer in the study and development of strategies in the most difficult cases.

Bernabeu Institute


For families of color, the Instituto Bernabeu offers a complete guide with all the assisted reproduction solutions available.


Who said being a mother was easy? It's a whirlwind of emotions that begins long before we have our baby. We make the decision. She's smiling from ear to ear because she's dreamed of being a mother since she was little, and I, who didn't particularly care about being a mother, am starting to get excited too, because it's the most beautiful thing we're going to do together. 

We know it's not an easy path. Our friend Shantal had her daughter after the transfer of the second and only embryo she had obtained through IVF. Two embryos were obtained and one of them did not implant. That's why we turned to the Instituto Bernabeu, a gay-friendly clinic that gives us confidence. Thanks to theirMaternity guide for lesbian, bisexual and transgender women,we solved many of our doubts.   

The clinic is aware that today there are different family models beyond the traditional model. And that's why they try to address some of the concerns that arise when considering motherhood with two moms. They explain how to choose the best clinic and the techniques we have to make the dream of motherhood a reality. 

The guide has a special section on the importance of choosing thesperm donorthe most suitable, with the assurance that all have passed the most stringent medical, psychological and genetic tests to be candidates. In fact, only 9% of applicants pass the rigorous health checks. The IB has itsown bankfrom more than 1,100 seminal samples to assign the one with the greatest physical similarity to the patients. Furthermore, thegenetic compatibility test(TCG), which analyzes and detects between 3,000 and 600 hereditary diseases, is carried out free of charge.


The guide presents the different assisted reproduction techniques available to couples: insemination with donor sperm;in vitro fertilization(IVF) with donor sperm; IVF with double donation; or adoption of embryos. And theROPA method(reception of eggs from the couple), a technique exclusively intended for lesbian couples. One provides the egg while the other will ensure the gestation of the baby of both, allowing them to experience motherhood intensely. 

Instituto Bernabeu has clinics in Alicante, Madrid, Palma de Mallorca, Cartagena, Albacete, Elche and Benidorm and the first international clinic in Venice. He has nearly four decades of experience and patients from 167 countries entrust him with their reproductive care.

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