- Oncology: a pioneering technique to preserve the fertility of some children with cancer
- Reproduction: A step closer to restoring fertility after suffering from childhood cancer
"Someday I want to have three children" ... Angela (21 years old) looks forward to a not too distant future. He jokes with the ages: "The first at 26, the second at 28 and the third at 30". Smile. He knows better than anyone that life cannot be planned so much, but he fantasizes about the idea and who knows, "with work, stability and a good husband" (he comments with great grace), he may be able to meet those very marked times.
He is also aware that if he can think about this exciting project, it is thanks to the preservation of fertility that doctors recommended five years ago. Paradoxes of life. At 16 he was diagnosed with a Hodgkin lymphoma and at the same time he had to assume the words cancer or chemo, in the midst of confusion, fear and adolescence, he also had to consider a maternity while still playing with dolls.
I knew his road map. In theory, he was going to need about eight months of chemotherapy and had been told that this treatment could reduce his chances of conceiving. "I reconsidered and thought that I wanted to be a mom in the future," so in the hospital where they were taking their case, Gregorio Marañón de Madrid, they indicated the steps before starting the sessions. "I had to prick myself every day in the gut [hormonal treatment of ovarian stimulation] for a couple of weeks. They managed to extract 11 oocytes that are now vitrified and preserved " waiting for her to want to use them.
This process extends about a month, which is the time that the chemo must be delayed. As Federico Pérez Milan, head of the assisted reproduction section of the Obstetrics and Gynecology Department at Gregorio Marañón, points out, "gamete precursor cells (ovules and sperm cells) have special sensitivity to agents that have been designed to destroy tumor cells." . For this reason, the ovules are removed before exposure to cancer treatment, which means that this procedure can only be performed under one condition: that the patient does not urgently require therapy . The logical order of the factors should be remembered: "No strategy should compromise the effectiveness of cancer treatment," says the specialist.
The aftermath of cancer
Luckily, Angela's case did not imply this haste. "Hodgkin lymphoma is one of the cancers that gives us more room to do ovarian stimulation. It is a very good survival and progress was slow," recalls one of the oncologists who treated her, Carmen Garrido.
In Spain, approximately 1,400 tumors are diagnosed every year in children under 18 . The good news is that "the five-year survival we are considering in our country is around 75-80% (compared to 55% in the 80s)," said Mara Andrés, a pediatrician at the Children's Oncology Unit of La Fe Hospital Valencia.
A hopeful reality that supports a face b: the long-term consequences of the treatments applied. "Sometimes at the pulmonary, renal, thyroid and also ovarian and testicular levels," says Dr. Andrés. "As they have reached higher rates of cure and there have been advances in the field of reproduction, specialists have begun to worry more about their quality of life in the long term. And this happens to consider their desire for reproduction" .
In the words of the gynecologist, "fertility preservation procedures are one of the tools that try to minimize the impact of tumors and their treatment on the patient's future quality of life. Any cancer disease can truncate the individual's expectations, especially if it modifies a lot and irreversibly its life project, such as the reproductive one. "
As much as possible, it is about making cancer just a memory and in this line, Garrido recognizes that "pediatric oncologists are thinking that apart from curing cancer in the first place, we have to think about the effects secondary . "
As he says, "there is still little information about the possible impairment of fertility and the alternatives available. In fact, less patients arrive at the preservation of oocytes than they should."
Not only does she say it. A national survey published in 2017 in the journal Anales de Pediatría concluded that 76% of the members asked (of the Spanish Society of Pediatric Hematology and Oncology) did not know of any guidance on fertility in children and adolescents. As Mara Andrés points out, "it is because there is none for this part of the population, but for adults."
Angela was clearly exposed to the situation and the alternatives, but "I know people of my age who was a year and a half of treatment, nobody told her about the possibility of preserving their fertility and they may have lost their only opportunity ." In this sense, adds the oncologist Garrido, "several publications collect the complaints of survivors who would have liked to receive such information. To them, this impossibility supposes a burden on their emotional life and sometimes psychological disturbances."
In this regard, Dr. Andrés remarks, "Sometimes, the lack of referral is not only a consequence of the lack of information but also of administrative obstacles and care overload to be able to offer this technique in a real way and in the appropriate time without compromising the start of treatment ".
I know people my age who was a year and a half in treatment and nobody told him that he could preserve his fertility. They may have lost their only chance.
Angela, 21 year old patientIt is estimated that in 25% of tumors that occur in children and adolescents there is a very high risk of significantly affecting their chances of pregnancy. The rest will have a fertile life comparable to the general population. That 25% includes "patients who are going to receive high-dose pelvic or craniospinal radiotherapy, those who are going to have a hematopoietic precursor transplant and those who will have a high-content treatment of alkylating agents (such as Ewing's sarcoma ) ", argues the specialist of the Hospital La Fe. In all of them," your fertility will be compromised between 75% and 90% ".
Each case is analyzed individually, taking into account several factors such as the diagnosis, the necessary therapies, the risk of toxicity that entail according to the age of administration, the urgency of the treatment, family and clinical circumstances, the prognosis ... From there, doctors meet with the patient's parents and expose the high risk of sterility and the options available.
When it comes to a child, semen cryopreservation is, today, the method approved in Spain. The problem is that it can only be applied if the patient is sexually mature. Otherwise, it is unfeasible. For these cases, work is being done at the experimental level in the conservation of testicular tissue. It consists of extracting it by biopsy and freezing it before starting the cancer treatment. The objective would be that in the future, the patient can undergo a self-transplant of the tissue in their own testicles and once inserted, restart the maturation of the reproductive cells and be able to produce mature sperm to fertilize.
The Netherlands and Belgium are pioneers in this type of cryopreservation. In Spain, it is also being carried out by the Fertility Preservation Unit of the La Fe Hospital in Valencia, framed within a research project. "It has not yet been reimplanted in humans, but in mice and primates with good results," says Mara Andrés. That is, this technique is still in very early stages of study and in order not to create expectations, "we have to explain very well that if we proceed to freeze the testicular tissue of a patient, it does not mean that we will be able to use it, but in some years the technique finishes developing effectively and safely, we will have that window open ".
In the case of girls, there is the cryopreservation of oocytes that Angela underwent. It consists of "stimulating the ovaries (between 10 and 12 days), producing a development of multiple follicles that must then be extracted vaginally in order to freeze them so that at any given time, these germ cells can be used through assisted reproduction techniques" , explains Federico Pérez Milan. As in children, this procedure requires that "the patient have menstruation and their cycles are more regular."
If this is not the case or when the onset of treatment cannot be delayed, there is a way that is about to become a common clinical practice in Spain: cryopreservation of the ovarian cortex. Since it was first tested on a sheep 15 years ago, its application in humans has grown exponentially. The scientific literature has verified its ability to achieve the restoration of hormonal function and has echoed the birth of 150 babies after reimplantation of ovarian tissue worldwide. It consists of the removal of ovarian tissue with a minimally invasive laparoscopic procedure. Ideally, "we should agree with another intervention that requires sedation, for example, when placing the catheter for chemotherapy," says the specialist of La Fe de Valencia. Then, this tissue is preserved until the patient poses the willingness to use for reproductive purposes. That is when you can proceed to the reimplantation of this material.
If we freeze a patient's testicular tissue, it does not mean that we will be able to use it, but if in a few years the technique finishes developing, we will have that window open.
Mara Andres"The hormonal function resumes between 90 and 120 days later. If the operation is successful, the woman will recover her fertility and may become pregnant naturally or using assisted reproduction treatments," says José María Rubio, section chief of the Assisted Human Reproduction Unit of La Fe Hospital in Valencia.
The San Joan de Déu Hospital in Barcelona was the first to bring a newborn to the world after ovarian tissue transplantation in 2012. The pregnant woman was an adult woman who had to have her ovaries removed because of a tumor. This center was also the first to start storing pediatric ovarian samples. An idea that was taken later (in 2009) by La Fe Hospital in Valencia through a specific program to cryopreserve the ovarian cortex in underage girls with cancer. " We have 105 frozen samples. Of these, more than half (60%) come from other autonomous communities," says the specialist from the Valencian center. "Our elderly patient is now 23 years old and has not yet requested reimplantation."
Only in Belgium and the United Kingdom were babies born from samples collected in pre-puberty stage due to a disease that entailed a high risk of sterility. In the words of Mara Andrés, "there are other diseases that are also candidates for this type of techniques, especially those that involve a transplant of hematopoietic precursors, such as sickle cell anemia ."
Unlike the freezing and reserve of testicular tissue, "the ovarian is becoming less and less experimental to the point of becoming a clinical offer in many countries like Israel," says the gynecologist Gregorio Marañón. Precisely in the Community of Madrid work is being done in this area. It is expected that "by the end of the year or early next year we will be able to offer this service instead of referring the patient to the Hospital La Fe in Valencia," sources of the Ministry of Health assure this newspaper.
For Mara Andrés, "cryopreservation of the ovarian cortex would be the ideal choice, and the only one that can be offered to pre-pubertal patients. It does not delay or interfere with cancer treatment , it is simpler than cryopreservation of oocytes and can even be considered when it has been given some chemo that may have affected the ovaries very little. "
As for the possibility of reintroducing malignant cells in this autotransplant, another of the patients' fears, "in solid tumors the risk is considered to be very small. We have highly sensitive techniques to detect signs of cancer in the sample." However, it is not indicated in leukemia . Despite this, "we continue to do the extraction because in about 10 or 20 years we can probably work it in the laboratory to get healthy oocytes to mature and bind them to the sperm. Today it seems like science fiction, but it will be possible."
What is unquestionable is that the advances of recent years and those that are on the way are making it possible to think about the healing of the patient without forgetting his quality of life and his desires for the future. On one occasion, recalls the gynecologist of the Madrid hospital, "a young adult told me that raising her options to preserve her fertility made her see that she was actually going to cure the disease." However, other options such as egg donation or other non-biological forms of parenthood can also be considered.
At the moment, Angela has her motherhood safeguarded. He is about to finish teaching and thinking about the three children he wants to have later. "I'm glad I agreed to freeze and reserve my 11 oocytes," he says. They are insurance for your life project with large family.
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