Breakthrough study demonstrates the 're-awakening' of the ovaries and achieves pregnancy in woman with premature ovarian failure using stem cells

LONDON, July 6, 2020 /PRNewswire/ -- IVIRMA, a global network of fertility clinics and world-leading pioneer in fertility research, are presenting a breakthrough study at the 36th 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.1 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).1

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',1 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.2 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 Study1

• 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 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.3 (Presentation on 6th July at 10:30 CEST)
• 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.4 (Presentation on 7th July at 10:10 CEST)
• 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.5 (Presentation on 8th July at 14:10 CEST)

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 386 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.7

More about the ASCOT technique development: 3 babies and 6 pregnancies achieved so far in low-responder patients

To date, 3 babies and 6 pregnancies have been achieved using the ASCOT technique for ovarian rejuvenation in low-responder patients with low ovarian reserve, pioneered by IVIRMA Global. The technique involves transplanting bone marrow-derived stem cells (BMDSC) into the ovarian artery, achieving a partial reversal of ageing of the ovary, the organ responsible for ovulation, and activating the dormant follicles that would otherwise remain arrested in the ovary. After its first phase in animal models to test the effectiveness of the technique with stem cells, this study went to its second phase in low-responder patients. A total of 20 patients had their stem cells mobilized, extracted from peripheral blood and implanted back into the ovary in order to reverse the ageing process and activate the dormant follicles. This technique has improved ovarian function biomarkers in 81% of low responder patients. In addition, spontaneous pregnancies occurred. In view of the success of this phase, the next stage was undertaken, which consisted of recruiting women under 38 years of age, this time with early ovarian failure (a situation with a worse reproductive prognosis that of low responders). From here the above-mentioned study arose.

IVIRMA Global and IVI London, UK

IVI was founded in 1990, as the first medical institution in Spain fully dedicated to Assisted Reproduction. Since then it has helped with the birth of more than 200,000 babies thanks to the application of the latest Assisted Reproduction technologies. In early 2017, IVI merged with RMANJ, becoming the largest Assisted Reproduction group in the world. It currently has more than 65 clinics in 9 countries and is the leading centre for Reproductive Medicine. In 2016 IVI opened its doors in London, located in the heart of the medical district.www.rmanetwork.comhttps://ivi-fertility.co.uk/

References

1. N. Pellicer De Castellvi, S. Herraiz, M. Romeu, S. Martinez, A. Buigues, I. Gomez-Segui, J. Martinez, A. Pellicer. (2020). ESHRE 2020. Abstract. 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. Available online. https://www.eshre.eu/ESHRE2020/Programme/Searchable#!abstractdetails/0000615810 (Last accessed: 05 June 2020)
   
   
2. L. R. Newson and R. Lewis. (2018). British Journal of General Practice 2018. Premature ovarian insufficiency: why is it not being diagnosed enough in primary care? Available online. https://bjgp.org/content/68/667/83#:~:text=POI%20is%20very%20common%3B%20it,patients%20with%20POI%20are%20adolescents (Last accessed: 05 June 2020)
   
   
3. M.J. Soriano, J. Martínez, R. Lopez, S. Herraiz, C. Díaz-García. (2020) ESHRE 2020. Abstract. A new strategy to assess safety of controlled ovarian stimulation protocols for oocyte vitrification as a fertility preservation technique in breast cancer patients. Available online. https://www.eshre.eu/ESHRE2020/Programme/Searchable#!abstractdetails/0000616940 (Last accessed: 06 June 2020)
   
   
4. L. Bori, F. Meseguer, M.A. Valera Cerdá, L. Alegre, A. Tejera, J. Remohí, M. Meseguer. (2020). ESHRE 2020. Abstract. A universal algorithm is available in last generation time-lapse incubators: embryo score provided by the KIDScoreD5 is strongly correlated with chromosomal status and clinical outcomes. Available online. https://www.eshre.eu/ESHRE2020/Programme/Searchable#!abstractdetails/0000615160 (Last accessed: 05 June 2020)
   
   
5. A. Cobo, J. Giles, S. Paolelli, A. Coello, J. García-Velasco, J. Remohí. (2020). ESHRE 2020. Abstract. Oocyte survival and clinical outcome is impaired in young endometriosis patients after fertility preservation. Available online. https://www.eshre.eu/ESHRE2020/Programme/Searchable#!abstractdetails/0000618100 (Last accessed: 05 June 2020)
   
   
6. IVI London. Success Rates 2018. https://www.ivi.uk/assisted-reproduction-treatments/success-rates/ (Last accessed: 05 June 2020)
   
   
7. IVI London, Data on file, 2020.

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