London, UK, 6^th July 2020. IVI RMA, a global network of fertility clinics and world-leading pioneer in fertility research, are presenting a breakthrough study at the 36^th Congress of the European Society of Human Reproduction and Embryology (ESHRE) today, demonstrating the possibility of ‘re-awakening’ the ovaries in women under 40 (38 years and below) with the lowest reproductive reserve at the ovarian level. The ASCOT technique (involving infusion of stem cells in the ovarian artery), which has recently been shown to be successful in low-responder patients, has now shown it can achieve pregnancy in a woman with premature ovarian failure (POF).

The study, ‘Bone marrow derived stem cells restore ovarian function and fertility in premature ovarian insufficiency women. Interim report of a randomized trial: mobilization versus ovarian injection’, which is still ongoing, includes two study arms: one using the ASCOT technique, that is, the infusion of stem cells in the ovarian artery and, second, a less invasive option consisting of mobilising the stem cells, and allowing them to reach the ovaries through the bloodstream directly. The preliminary results have shown that ovarian follicle development was achieved in both groups, with some patients re-starting menstruation, and a decrease in menopausal symptoms. As a result of this procedure, embryos were obtained in 2 out of the 10 participants, and even one pregnancy through the ASCOT technique was achieved.

Dr. Diaz, Medical Director, IVI London, a leading fertility specialist and co-pioneer of the world’s first womb transplant, commented, “We are truly excited by these very promising results achieving ovary re-awakening and pregnancy using stem cells in a woman who previously may not have had the option to conceive using her own eggs. We continually strive to pioneer on the cutting-edge of fertility research, as we know how harrowing it can be for every person struggling to conceive. These new techniques may give us potential new options for women with premature ovarian failure, in addition to those with low ovarian reserve.”

It is estimated that 1 in 100 women under 40 years of age suffer from premature ovarian failure (POF) in the UK. 2.5% of all patients with POF are adolescents. This premature cessation of ovarian activity is one of the most challenging scenarios in terms of reproduction and can be devastating. Now, thanks to the findings of this study, led by Dr. Sonia Herraiz, researcher at the IVI Foundation-IIS la Fe, Spain and Dr. Nuria Pellicer, gynaecologist at Hospital la Fe in Valencia, Spain, there might be hope for women suffering from this fertility issue.

Dr. Nuria Pellicer, Gynaecologist, Hospital la Fe, Valencia, Spain added, “So far, we obtained embryos in 2 of the 10 patients included and one 37-week pregnancy in the ASCOT arm, in patients with almost no chance of successful pregnancy with classic in vitro fertilisation procedures. We found that both arms promoted the development of follicles, and some patients have even recovered their menstruation, thus reducing menopausal symptoms However, these are preliminary results of an ongoing study, so we remain cautious until the study is complete. We aim to develop a technique that is as minimally invasive as possible over time and standardise it so that it can be implemented in all our clinics. We would like to make it possible to offer any woman who wishes to become a mother the possibility of doing so, even when her reproductive circumstances are unfavourable.”

“This is 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, however difficult the reproductive prognosis may seem”, concluded Dr. Herraiz, researcher at the IVI Foundation-IIS, la Fe, Spain.

More About the Study

• The ovarian reserve is made up of primordial follicles, called “sleeping” follicles. These are very small follicles that are stored in the ovary at the time when the ovary is formed, and they constitute the ovarian reserve. Every month, around 1,000 of these follicles are activated and begin to go through all the phases of development until they reach the mature egg stage, in a process that takes months. Many degenerate throughout this development process until only one or two remain. The techniques used in the study enable these follicles (which, on their own, either do not become activated, or if activated, end up degenerating in the first stages of growth), to grow and develop. This whole process takes place inside the ovary.
• There are currently 10 participants with POF in the study, 6 of which were treated using the existing ASCOT technique, and 4 were treated using the less invasive mobilisation of stem cells into the bloodstream. All are 38 years old or below. Following these interim results, the study will expand to include more women with premature ovarian failure.
• The preliminary results have shown that ovarian follicle development was achieved in both groups with a decrease in menopausal symptoms. As a result of this procedure, embryos were obtained in 2 out of the 10 participants, and even one pregnancy through the ASCOT technique.
• Until now, previous studies only delivered stem cells directly into the ovary, but results obtained in this study suggest that this invasive step may not be necessary, and that the cells and the factors stem cells secrete are capable of reaching their target through the circulatory system, a process that is much less invasive and easy to apply at any clinic.

In addition to this research, IVI are presenting three more studies at the ESHRE Congress:

• The use of Artificial Intelligence in embryo selection. The technology and software used in this study- that IVIRMA Global has participated in developing- analyses and classifies embryos based on their quality thereby, increasing the probability of achieving successful pregnancy.
• The impact of Endometriosis on the fertility levels of younger patients. The findings of the study confirm that the condition affects the ovarian reserve and quality in these patients and early fertility preservation through egg vitrification increases their chances of pregnancy.
• The impact of controlled ovarian stimulation (COS) protocols on the proliferative potential of breast cancer cells. It is known that chemotherapy affects the fertility of a woman undergoing breast cancer treatment, and therefore patients choose fertility preservation (oocyte vitrification) to achieve a successful pregnancy in the future. There was still limited evidence to understand the safety of new protocols using aromatase inhibitors such as Letrozole in COS for women with breast cancer. This initial study, which was conducted in mice, shows promising results on the safety of such a procedure without causing the tumour cells to proliferate, providing reassurance for women with breast cancer who may want to have fertility preservation. However, more research is yet to be conducted to validate the data.

These new techniques and other research conducted by IVI is translated and applied to the treatments available in their clinics across the world, which is in turn reflected in the achieved results. The London clinic has achieved 71.4% clinical pregnancy rates per embryos transferred in women under the age of 38 and recent data shows that with PGT-A genetic screening the evolutive pregnancy rate is 57% in women undergoing treatment at IVI London as compared to the national average of 42%.⁷ Furthermore, 100% of these pregnancies have been achieved through single embryo transfer, eliminating chances of multiple pregnancy and the complications that arise with it.