Low responders are one of the current challenges of assisted reproduction techniques. It is estimated that between 9-14% of patients who undergo an IVF cycle have a low response.

This pathology is increasing in recent years due to delayed motherhood. Unfortunately, it is well established that low response is associated with high cancellation rates and lower rates of chance of pregnancy relative to patients with a normal response.

Personalized stimulation strategy

One of the main causes of low ovarian reserve is age, although it is true that biological age does not always correspond to ovarian age. There are women who are born with a smaller number of oocytes and others who develop many follicles in each menstrual cycle.

At CdelaF we apply personalized and differentiating stimulation strategies, always with the aim of selecting the optimal cycle that ensures the best egg, which entails great knowledge of the variability of menstrual cycles and a medium-term strategy. Slowly but surely.

What is endometriosis and how does it develop?

Endometriosis is a disease that generally causes two types of problems: pain or infertility. Before we dive in, let’s focus on the female reproductive anatomy, which can be divided into 3 key organs:

• Ovaries – This is where eggs develop and are released during ovulation
• Fallopian tubes – Once the egg is released from the ovary, it travels down the fallopian tubes where it can come into contact with sperm to become a fertilized embryo.
• Uterus : Once the embryo has passed through the fallopian tube, it is released into the uterus. Specifically, this is where the embryo implants into the inner lining of the uterus, providing nourishment so the embryo can develop into a healthy fetus.

Endometrial Cells

To understand endometriosis, it is helpful to understand the lining of the walls of the uterus, the endometrium, and the cells it is made of (known as “endometrial cells”). Endometrial cells are special: they grow abnormally fast in the presence of estrogen. When they grow, they create a thick inner endometrial lining of the uterus and this helps ensure that an embryo can implant into its wall. An embryo needs good implantation to ensure that it receives nourishment and can develop into a fetus. When endometrial cells escape, that is endometriosis.

Endometrial cells are useful when they are contained in the uterus, but when they escape from the uterus, they wreak havoc. When these cells implant and establish themselves in other organs, they cause inflammation and local damage. In fact, this is endometriosis.

The most common places where the endometrium usually adheres are:

• The ovaries
• The Fallopian Tubes
• The ligaments of the uterus
• The vagina
• The intestine
• Although with a lower incidence, it is also possible to find foci of endometriosis in the urinary system, in the ureter, the kidneys or, exceptionally, in the lungs.

Symptoms of endometriosis

The main symptoms of endometriosis are related to pelvic discomfort and infertility.

Other symptoms that can determine endometriosis are:

• Menstrual cramps
• Pain during and after sexual relations
• Discomfort in the abdomen and/or intestine
• Discomfort when urinating
• Bleeding between periods
• Constant menstruation
• Painful fatigue syndrome
• Tiredness and/or fatigue

If some of these symptoms are present in your body, at CdelaF we offer you the appropriate diagnosis to know if you suffer from this disease, as well as the timely treatment for endometriosis.

How endometriosis impacts fertility

The presence of endometriosis can make it difficult for a woman to conceive. Specifically, endometriosis can interfere with reproductive components and functions such as:

Reduced egg count

By implanting and “eating” on the ovaries, endometriosis can reduce egg count. Antral follicle counts (AFC) and anti-Müllerian hormone (AMH) levels are two commonly used indicators of ovarian reserve, and recent studies have suggested that patients with endometriosis have reduced ovarian reserve, even before they are done. attempts to eliminate endometriosis.

Surgery to remove endometriosis in the ovaries can also further reduce ovarian reserve. Endometriosis adheres closely to normal ovarian tissue and some of the normal ovarian tissue is inevitably removed during removal of endometriosis from the ovary. For patients with good ovarian reserve, these changes may not affect the likelihood of having a successful pregnancy, but for patients with already low reserves, particularly those who will need IVF, surgery may have a significant negative impact.

Reduced egg quality

Additionally, endometriosis can create a microenvironment that can worsen egg quality. A meta-analysis of 22 studies and 6,760 IVF patients showed that patients with endometriosis have lower fertilization rates and lower implantation rates per embryo than other patients (in this case, those with blocked tubes). Additionally, a small study shows that embryos created from eggs from donors with endometriosis are much less likely to implant than embryos created from eggs from donors without endometriosis.

Fallopian tube

Endometriosis and related scarring around the fallopian tubes can create blockages or abnormal functions that prevent the egg or embryo from moving through the tube or the sperm from moving up. This may prevent the sperm from fertilizing the egg or, if fertilization occurs, prevent movement of the resulting embryo through the tube, increasing the risk of a tubal (ectopic) pregnancy. In a recent study of more than 14,000 women, women with endometriosis were 2.7 times more likely to have an ectopic pregnancy than women without endometriosis. Although the absolute numbers are small, ectopic pregnancies can be very dangerous.

Uterus

When endometriosis cells colonize other organs, they cause inflammation. Since the uterus is part of a larger reproductive ecosystem, when other organs become inflamed, so does the uterus. This can affect the ability of the uterus to allow an embryo to implant and receive nourishment. An interesting design study showed that recipients of embryos from donors with endometriosis are at least 20% less likely to have embryo implants than recipients of embryos from donors who did not have endometriosis.

Sperm

Regardless of where endometriosis exists, it causes inflammation, and if sperm swim near the region of inflammation, their motility (ability to swim) and function may be affected. The percentage of sperm with DNA damage doubles after exposure to pelvic fluid from patients with endometriosis compared to sperm exposed to pelvic fluid from women without endometriosis.

How common is endometriosis and who is at risk?

Endometriosis affects approximately 1 in 10 women during their reproductive years. Among patients with infertility, endometriosis is at least twice as common, affecting 20 to 70% of women with infertility, according to the study.

However, the true prevalence of endometriosis can be difficult to determine because there is generally little effectiveness in identifying it in a timely manner, if it is detected at all. Most women with endometriosis report that they were consulted at least five times before receiving a diagnosis with an average delay of 10 years. This is because gynecologists and patients rule out or “normalize” menstrual cramps and other nonspecific gastrointestinal symptoms that may be a sign of endometriosis: 75% of the women studied were first seen by a general gynecologist.

What can we do?

Personalized ovarian stimulation treatments with antral enhancement may slightly increase the number of eggs, but substantially improve the quality of the eggs recovered. In addition to personalizing the protocols, monitoring and the ability to adapt to the evolution of the cycle of the patient with endometriosis is essential for the success of the treatment.

In other cases, the patient with endometriosis needs to resort to minor surgeries to improve uterine anatomy and functionality and try to ensure the implantation of the embryo as much as possible.

The different assisted reproduction techniques help to achieve pregnancy, however, an individualized strategy is necessary from the moment the disease is diagnosed and that lasts beyond achieving pregnancy. Our goal is to treat the disease to limit its degree of impact in terms of fertility, taking advantage of the different possibilities that reproductive medicine offers us in case we do not achieve a pregnancy naturally.

At CdelaF, endometriosis is treated in a global way and with absolutely personalized strategies.

Genetic infertility is caused by some alteration in the DNA sequence of the woman or man who is trying to have a child. Depending on the type of genetic anomaly, it is possible to differentiate between:

• Aneuploidies: numerical or structural alterations of the chromosomes
• Genetic mutations: defects in one or more genes

As an introduction, let’s start by differentiating what chromosomes are and what genes are. As for the chromosomes, you can imagine that they are as if they were structures where there is information, like bookshelves where the books are, which in this case would be the genes. That is, there are many genes on a chromosome. Therefore, sometimes there is an alteration of only one gene, other times there is an alteration of the entire chromosome, and therefore of all the genes on that chromosome.

Sometimes, future parents are not aware that they are carriers of some genetic alteration until they begin to have difficulties achieving a pregnancy. The CdelaF specialized genetics unit aims to diagnose and prevent chromosomal anomalies and genetic diseases in the embryo before it is implanted, avoiding repeated abortions, implantation problems and possible genetic diseases.

From the reproductive genetics unit we offer our patients the most advanced tests in the field of the human genome and complete advice on the diseases, syndromes, mutations that they detect.

Repeated failures in IVF treatments generate great frustration for both patients and assisted reproduction professionals. There are several factors that can lead to the failure or failure of the IVF technique. The main ones are the lack of eggs, the failure of fertilization of the eggs and therefore the absence of embryo creation, implantation failure or the difficulty of carrying the pregnancy to term.

CdelaF specialists will be able to explain to you the causes of implantation failures and why the final goal of IVF treatment is not reached: a healthy baby at home.

Possible subtle causes of repeated implantation failure

It is well known that the success of an implementation depends on:

• The quality of female and male gametes
• A healthy uterine cavity
• embryonic quality
• Endometrial receptivity
• A technique and a suitable moment for embryo transfer
• A correct interaction between endometrial and embryonic factors during the implantation window (“good embryo-endometrial dialogue”)
• Correct hormonal support

Deployment window

In recent years, special attention is being paid to the implementation window. This is the period of time in which the uterus is most receptive to the embryo. Thanks to innovative genomic and proteomic studies, we can analyze the implantation window of each woman and determine with greater effectiveness and efficiency the moment of embryo transfer to increase the probability of implantation and therefore pregnancy.

Anatomy of the uterine cavity

Hysteroscopy is one of the most important diagnostic tests in patients with repeated implantation failure in order to rule out intracavitary pathologies that could have gone unnoticed with conventional diagnostic means (2D and 3D transvaginal ultrasound, hysterosalpingography and hysterosonosalpingography, nuclear magnetic resonance). Hysteroscopy allows visual confirmation of the state of the cervical canal and uterine cavity.

It is very important to identify and rule out as much as possible in order to determine the possibilities of intervention in patients with repeated IVF failures.

At CdelaF we offer you a comprehensive treatment evaluating:

• Alterations in endometrial receptivity ranging from hysteroscopy to evaluation of an endometrial scratch
• Combined immunotherapy treatments, with glucocorticoids or heparin in specific cases
• Sperm DNA fragmentation
• Assisted Hatching
• DGP
• Transfer in blastocyst stage
• Surgical treatment of endometriosis, hydrosalpinx or fibroids
• Cervical anatomy study for difficult embryo transfer cases
• Luteal phase support based on personal hormone levels
• Support to improve lifestyle
• emotional support

Infertility can have a very diverse origin: 30% is due to female causes, another 30% to male causes and 20% has mixed causes, that is, both members of the couple present alterations.

The remaining 20%, however, has an unknown origin. This means that, after having done all the usual diagnostic tests, the results are normal and it is unknown what may be altering the female or male reproductive system to prevent pregnancy.

Causes

Since we are talking about infertility of unknown origin, it is difficult to explain the real reasons why a couple does not achieve pregnancy.

However, experience in assisted reproduction treatments has detected some alterations that could be the causes of this difficulty in conceiving. We explain them below:

Chromosomal alterations in the egg

• The number of aneuploidies or genetic mutations in a woman’s eggs increases with age. Although the woman has normal ovulatory cycles, it is possible that the oocyte quality is affected and they are not capable of giving rise to embryos that implant and develop normally.

Alterations in the embryo

• By fertilizing the eggs with sperm in the laboratory, it is possible to observe the morphology of the embryos and their development. Those embryos with asymmetric cells, fragmentation, multiple nuclei or that grow slowly are considered of poor quality and, therefore, have a greater probability of not developing and giving rise to implantation failures or biochemical abortions.

Implementation failures

• In order for the embryo to adhere to the uterine wall and begin its development, it is necessary that the endometrium be receptive and that there be perfect synchronization between the embryo and the endometrium. An altered implantation window could lead to implantation failure and inability to achieve pregnancy.

CdelaF is an expert in the treatment of infertility of unknown origin. After several attempts with assisted reproduction techniques, it is very possible that there is a multifactorial cause that makes pregnancy difficult. At CdelaF we believe that infertility always has a reason. Given this diagnosis, we focus our efforts on investigating the causes using all available diagnostic techniques until we discover the reason.

At CdelaF we believe that infertility always has a reason

CdelaF is one of the few fertility clinics that studies, diagnoses and treats the immunological factors involved in the reproduction process. Immune system disorders and autoimmune diseases can cause infertility in both men and women. These disorders are difficult to diagnose, but approximately 20% of cases of infertility of unknown origin are due to some type of immune disorder.

Infertility of immunological origin has different ways of manifesting itself: it can destroy the gametes themselves, prevent embryo implantation or even cause repeated spontaneous abortions.

Types of immunological infertility

Some of the types of immunological infertility that we treat are:

• Antisperm antibodies
• Hereditary Thrombophilias
• Antiphospholipid syndrome
• Alloimmune Infertility

At CdelaF, we advise you so that, once the altered immunological factors are identified, treatment and monitoring begins through specialized and individualized protocols for each patient.

It is believed that male factor infertility impacts between 30 and 50% of all cases in which couples have problems getting pregnant. There may be a variety of underlying factors that contribute to male factor infertility, and the reality is that some may herald a deep and troubling problem with a man’s health. Therefore, male factor infertility may be a symptom of something more concerning that needs to be addressed.

But it is important to know that although many cases can be resolved using the fertilization technique called ICSI (Intracytoplasmic Sperm Injection), often less invasive and less expensive approaches can give the same result.

To properly characterize the underlying problem and consider alternative approaches to an IVF cycle, men should be seen by an experienced fertility urologist trained in male anatomy (Reproductive Urologist or Andrologist). The reality is that male factor infertility is often detected by reproductive endocrinologists, who are doctors who specialize in fertility, but at the end of the day they are gynecologists.

At CdelaF we help with a number of crucial issues including:

• Differentiate between a reproductive endocrinologist and a reproductive urologist
• Reading and interpretation of semen analysis
• The basics of IUI and IVF in the context of male factor infertility
• Lifestyle factors can affect a man’s fertility
• Identify and treat varicocele
• Classifications and challenges in the treatment of azoospermia
• Exogenous Testosterone Use and Other Hormonal Imbalances
• Impact of advanced paternal age on fertility and offspring

CdelaF and our urology unit specialized in infertility and men’s health treats all possible prostate, urinary and hormonal pathologies that may compromise men’s fertility.

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