• Promising results are achieved in women under 40 with the worst reproductive scenario at ovarian level, thanks to the ASCOT technique (infusion of stem cells in the ovarian artery), which was already successful in low-responder patients
• The latest development shows the benefits of mobilizing stem cells in bone marrow and how, without injecting them, they reach the ovary themselves through the circulation. This process is less invasive and easier to apply
• Another finding shows the development in the follicles promoted by this technique, which has led to some women recovering their menstruation and therefore decreasing menopause symptoms

Approximately 1 in 100 women under 40 years of age suffer from premature ovarian failure. This means that the ovaries prematurely cease their activity, which is one of the worst situations in the field of reproduction, since some women who suffer from this pathology do not even menstruate.

Dr. Sonia Herraiz, researcher at Fundación IVI-IIS la Fe, and Dr. Nuria Pellicer, a gynaecologist at Hospital la Fe in Valencia, have led a study that gives hope to all these women who suffer from premature ovarian failure.

Progress made in the study on premature ovarian failure

As Dr. Pellicer explains: “Instead of administering the stem cells, which has been performed in previous stages of this research, the process consists of leaving them to reach the ovary on their own in order to provide their positive effects there. In both cases, either by administering the cells or by simply mobilizing them, the stem cell releases growth factors that stimulate the cells in the tissue where it will grow, proliferate or regenerate. In the case of the mobilization-only study arm, it is a less invasive procedure because cells are not administered, but rather, they are allowed to reach the damaged ovary”.

This work has been presented in the framework of the 36th Congress of the European Society of Human Reproduction and Embryology (ESHRE), in which the study population has been expanded and is no longer limited to low-responders, offering a possibility to women under 40 years of age who suffer premature ovarian failure and who until now could not gestate with their own eggs.

What does the ovarian rejuvenation technique consist of?

The ovarian reserve is formed by primordial follicles that create the ovarian reserve. Every month around 1,000 of these follicles are activated, passing through all the phases of development until they reach the mature egg stage, in a process that takes months. Similarly, many degenerate during the development process, leaving only one or two.

As Dr. Herraiz states, “this technique consists of allowing these follicles, which, as the ovary is damaged, are not even activated, or if they are activated, end up degenerating in the first stages of growth, to reach the mature egg stage, since we regenerate the environment or microenvironment in which they will grow and develop. This whole process takes place inside the ovary”.

Previous studies were limited to inserting the stem cells into the ovary, but the preliminary results obtained recently indicate that it may not be necessary to insert the stem cells into the ovary, but that the cells and the factors that they have secreted can arrive through the circulatory system, in a much less invasive and simple process, meaning it could be applied in any clinic.

“With this we aim to develop a technique that is as minimally invasive as possible and standardize it so that it can be implemented in all our clinics and offer any woman who wishes to become a mother the possibility of doing so, even when her reproductive circumstances are unfavourable or clinically unfeasible without the intervention of science, as is the case,” added Dr. Pellicer.

This work, still in development, has two study arms:

• One limited to the ASCOT technique, which is the infusion of stem cells in the ovarian artery, defined by the mobilization of cells, their extraction and subsequent insertion directly into the ovary.
• And another, less invasive arm, which consists of mobilizing the cells, but letting them reach the ovary from the bloodstream, to check if they have the same effects as when they are collected and injected.

“This is where the second important advance in our work lies, in which we have found that the mobilization technique is capable of making those ovaries work again and having follicles, so we have been able to demonstrate that both arms manage to promote the development of follicles, and some patients have even recovered their menstruation, thus reducing menopausal symptoms. However, we must be cautious, as these are the preliminary results of a study that is still in the developmental phase. So far, we have obtained embryos in 2 of the 10 patients included and one 37-week pregnancy in the ASCOT arm, in patients with almost no chance with classic in vitro fertilization procedures,” said Dr. Pellicer.

ASCOT technique: What is it and what does it consist of?

The ASCOT ovarian rejuvenation technique, of which IVI is a world pioneer, consists of the transplant of bone marrow-derived stem cells (BMDSC) in the ovarian artery. This technique allows the ovary, as the organ responsible for ovulation, to partially reverse its ageing process and activate the dormant follicles, which would otherwise remain undeveloped. This technique has achieved an improvement in ovarian function biomarkers in 81% of patients, becoming a reality for these women, both low responders and those who suffer early ovarian failure. In addition, this technique has already resulted in the birth of 3 babies and up to 6 pregnancies.

This technique had a first phase in an animal model that enabled the effectiveness with stem cells to be verified. It then had a second phase with low-responder patients, a total of 20, in which stem cells were mobilized, extracted in peripheral blood and implanted again in the ovary, with the aim of combating ageing by activating the sleeping follicles. As a result, spontaneous pregnancies have even occurred in women with low ovarian reserve after undergoing a bone marrow transplant. Given the success of the technique so far, we moved on to a third phase, which consisted of analysing women under 38 years of age with premature ovarian failure –a situation with a worse prognosis than in the case of low-responders. In this phase of the study, the implementation aspect that we have already mentioned was created.

Dr. Herraiz concludes: “A very encouraging line of research in which we will continue to work with a single goal: to improve assisted reproduction techniques and treatments in order to obtain the best results in the largest population group, however difficult the reproductive prognosis may seem”.

From rejuvenation to ovarian rescue

This process, which is popularly known as “ovarian rejuvenation”, consists of rescuing the sleeping follicles from the ovary –not rejuvenating them–, so it would be more appropriate to call this technique “ovarian rescue”. The stem cells activate this ovarian niche in order to rescue the follicles that are already present, so that they can grow and mature to finally provide mature eggs for the patients.