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Innovative Training Network in Female Reproductive Care

Periodic Reporting for period 1 - MATER (Innovative Training Network in Female Reproductive Care)

Reporting period: 2019-10-01 to 2021-09-30

Female reproductive care addresses the reproductive system, processes and functions at all stages of life. Although natural reproduction is often taken for granted, today, one in six couples face challenges in achieving pregnancy, and approximately 10-20% of reproductive-aged women are infertile. Reproductive diseases account for 20% of the global ill-health for women (WHO), thus demonstrating the unmet attention to, and the crucial need for improving technologies of female reproductive care that has a significant clinical and social burden.Female fertility is a highly complex process that relies on a restricted pool of oocytes, that, under a tight control of neuroendocrine and ovarian hormones, are regularly matured and released for fertilization followed by embryo development and attachment into the uterine lining that supports its growth until birth. Even slight temporal deviations in this sensitive path may lead to disturbances in oocyte maturation, failure in fertilization or implantation processes, miscarriage or, in most dramatic cases, to the birth of a handicapped child. Female fertility is strictly time-constrained and happens only within the limits of reproductive lifespan, cut by menopause. In natural reproductive aging, the oocyte pool begins to decline rapidly already at late thirties, coinciding with the decreased chances of having a healthy baby and increased risk of age-related infertility. Pregnancies in advanced age are also more prone to fetal chromosomal aberrations that can lead, for instance, to miscarriage or to the birth of a sick child. This is an alarming phenomenon as in the EU and other developed societies families are more often intentionally postponing parenthood due do career and other social responsibilities, thus increasing female age-related reproductive risks and creating profound clinical, social and financial burden.
MATER innovative training network consists of 5 academic and 5 industry partners with outstanding expertise in female reproductive genomics and medicine. Via joint supervision the network aims to train a new generation of 14 creative, entrepreneurial, innovative and ethically sensitive early-stage researchers (ESRs) in the field of female reproductive care. The planed research covers the female fertility from oocyte to a birth of a healthy baby. The research aim of the project is to contribute solving some of the most pressing challenges in female reproductive care by targeting the delicate issues like infertility and pregnancy complications, and devising novel ideas to treat them, avoid miscarriages and implement genetic technologies in prenatal diagnostics to prevent birth of children with chromosomal diseases. Innovation aims of the project are helping students to recognize and understand the ethical issues of their work, as well to prepare them for converting the novel knowledge and ideas into social and economic benefits. Reproductive medicine is an ethically complicated topic and in different European countries the legislation varies widely. Given the importance and complexity of the project, we are focusing on ethical issues, with the aim to provide not only new biological knowledge and innovative technologies, but also answers to important ethical questions. Therefore, the MATER project contributes to the future discussions, rules and legislation regulating reproductive medicine in Europe.
The biggest scientific achievements of the first reporting period are 2 peer-reviewed publications:
1. Pagnaer, T., Siermann, M., Borry, P. et al. Polygenic risk scoring of human embryos: a qualitative study of media coverage. BMC Med Ethics 22, 125 (2021). https://doi.org/10.1186/s12910-021-00694-4
2. Jaakko S Tyrmi, Riikka K Arffman, Natàlia Pujol-Gualdo, Venla Kurra, Laure Morin-Papunen, Eeva Sliz, FinnGen Consortium, Estonian Biobank Research Team, Terhi T Piltonen, Triin Laisk, Johannes Kettunen, Hannele Laivuori, Leveraging Northern European population history: novel low-frequency variants for polycystic ovary syndrome, Human Reproduction, 2021; deab250, https://doi.org/10.1093/humrep/deab250

In addition, half of the Fellows had the chance to present their projects and work carried out already in several national and international conferences, like the annual meeting of European Society of Human Reproduction and Embryology (ESHRE) by ESR2, the annual meeting of European Society of Human Genetics (ESHG) by ESR2 and ESR14. For the international conferences the topics included ’The views of health care providers on the scope of pre-implantation genetic testing: a systematic review’ and ’Genetic association analyses identify links between pelvic prolapse (PP) and connective tissue biology, cardiovascular and reproductive health’.

In 2021, we organized our first very successful winter school in collaboration with another H2020 project ERIN. The 3-day MATER/ERIN winter school “Reproductive Genetics and Genomics” took place on February 17th–19th, 2021. In addition to MATER partners (KU Leuven, University of Tartu, Karolinska Institute and IGENOMIX) the programme included lectures by researchers from Maatricht University, University of Copenhagen, Utrecht University, Vrije Universiteit Brussel, University of Warwick - all together 20 lecturers from 8 countries. The event had 436 registrants and 114-214 participants per session. The winter school was attended by all 14 ESRs.
The overarching aim of MATER is to strengthen the research excellence and innovation capacity at European level by empowering and encouraging ESRs, as well as the MATER network of academia and industry partners, to
build up knowledge and innovation base in the area of female reproductive medicine. The research objectives of the project are divided into three main subjects:
I) ‘Female fertility regulation: molecular mechanisms and implications for family planning’ (ESR1, ESR2, ESR3 and ESR4). Solutions the research seeks to provide:
- unique genetic testing algorithm for predicting woman's personalised risk for age related infertility;
- improved genetic diagnostics for severe endocrinology and infertility-associated diseases;
- adopting personalised reproductive medicine assisting women to make evidence based family planning decisions.
II) ‘Uterine microenvironment: fertility, infertility and promises of stem cell therapy’ (ESR5, ESR6, ESR7 and ESR8). Solutions the research seeks to provide:
- clinically relevant endometrial receptivity biomarkers improve personalised infertility diagnostics and therapy;
- well characterised endometrial stem cell cohorts help to establish autologous stem cell therapy for endometrial regeneration;
- endometrial microbiome studies have enabled establishing molecular testing for chronic endometritis.
III) ‘Embryonic and fetal development: novel biology with clinical relevance’ (ESR9, ESR10, ESR11, ESR12, ESR13)
- studies on bovine IVF embryo culture conditions on CIN have provided information for establishing more strict IVF quality follow-up;
- improved NIPT technologies include fetal CIN risk to avoid false results in prenatal diagnosis.
Additionally, the research of ESR14 focuses on the ethical issues of reproductive medicine, linking the previously mentioned research subject into a single topic which aims to provide not only new biological knowledge and innovative technologies, but to review and analyse the ethical, legal, policy and health-care issues related to reproductive medicine in EU.