Micheline Misrahi-Abadou: personalising infertility treatments

Micheline Misrahi-Abadou developed an early interest in medical research. Her passion for the field of human reproduction emerged during her second year of medical studies at the Necker–Enfants Malades Hospital. After beginning her medical internship in gynaecology, obstetrics and endocrinology, she obtained a PhD in biochemistry and molecular biology from Paris 6 University (now Sorbonne University). She chose to specialise in women's reproductive health and to investigate the causes of infertility, a field that, at the time, was both under-researched and under-funded. "At the time, not only did infertility attract little interest because it wasn't a life-threatening disease, but many also thought they already had the miracle solution with medically assisted procreation!" Micheline Misrahi-Abadou recalls.
 

Genetic causes

According to the World Health Organization (WHO), in 2023, infertility affected one in six couples in developed countries. In France, it affects 3.3 million people and with an annual increase of 0.3%, this syndrome, "not a disease", is becoming a public health issue. "However, reproductive medicine differs from other specialities in that it often treats infertility without always fully understanding the cause, even though 30% of causes remain unexplained," notes the researcher. As early as the 1990s, she began exploring the genetic factors of infertility, which have been shown to have a strong link. "Up to 31% of familial cases have been documented in women with premature ovarian insufficiency (POI), or 4% of women aged under 40." Then, 25 years ago, it was discovered that the FMR1 gene, responsible for causing fragile X syndrome in boys, is also responsible for 3% to 5% of POI cases.
 

The world's first cloning of reproductive genes

In 1987 and 1989, Micheline Misrahi-Abadou performed the first cloning of the human progesterone receptor gene and established the structure of the LH/hCG (luteinizing hormone/human chorionic gonadotropin hormone) receptor that controls reproduction. This earned her the French Foundation for Medical Research (Fondation pour la Recherche Médicale) award. She also cloned the human receptor for TSH, the thyroid-stimulating hormone. These landmark achievements laid the foundations for her research into the genetic causes of infertility, which she began in 1992. Micheline Misrahi-Abadou then set up a molecular genetics platform for infertility at Bicêtre Hospital, starting with these genes and gradually expanding.
 

The genomics revolution

Micheline Misrahi-Abadou began by identifying a small number of genes, including those for the receptors for LH and FSH (follicle-stimulating hormone). "Mutations in these genes revealed links to certain forms of infertility, but the research took a long time and involved only a limited number of patients. Gradually, our catalogue grew through my team's discoveries, along with those of other researchers around the world." The genomics revolution, driven by the advent of next-generation sequencing, transformed the field. It enabled rapid analysis of all 20,000 genes in a patient's genome and the identification of defective genes.

The molecular genetics platform for infertility has now been accredited by the French Ministry of Health as a national reference. National and international partnerships have supported the development of the large patient cohorts which are essential for identifying the genes responsible for infertility, "including around a hundred genes linked to POI, out of the estimated one thousand genes probably involved in human reproduction, a process fundamental to the survival of a species," stresses Micheline Misrahi-Abadou.
 

An unexpected link between infertility and cancer

Analysis of the largest European cohort of patients with POI has led to a surprising discovery: the involvement of DNA repair and meiotic genes belonging to the Fanconi pathway. "At the time, it came as a surprise to everyone, but today it seems obvious." The link lies in the unique stock of follicles formed before birth; premature degradation of this reserve could cause a defect in these repair genes (which are known as cancer susceptibility genes). This revelation has profoundly altered how patients are monitored, requiring a long-term, multidisciplinary approach to prevent or treat possible tumours. "The genes involved in follicular growth, metabolism and mitochondrial functions represent the other major families responsible for POI."
 

Personalising care pathways with targeted treatments

France has made significant progress in genomic medicine, notably through the French Genomic Medicine Plan which, due to Micheline Misrahi-Abadou's efforts, included POI as a sequencing priority for the genome in 2019. However, it is used by few practitioners due to a lack of medical education and the absence of recommendations from learned societies. Thanks to the first genetic maps of POI and diminished ovarian reserve syndrome in women established by Micheline Misrahi-Abadou in 2022 and 2024 respectively, both diagnosis and patient care are now evolving. "In late 2024, we succeeded in getting four international learned societies to change their guidelines for this condition. Until then, they had only recommended testing for the FMR1 gene. We also introduced next-generation sequencing into our routine diagnostics, with analysis of around one hundred genes (30% positive). This represents a major advance for patients." The researcher hopes to see a greater use of genomics for personalised care of unexplained POI.

For women with a diminished ovarian reserve, who account for 10% of patients undergoing medically assisted reproduction (MAR), the researcher has demonstrated the benefits of predicting treatment efficacy and personalising care, thereby avoiding unnecessary treatment. Given the 40% failure rate of conventional treatments, she stresses: "There is an urgent need to identify new treatments and predictive biomarkers of treatment response in order to avoid unnecessary suffering for couples and significant public health expenditure. The reproduction sector is still characterised by a one-size-fits-all treatment. We need to personalise care pathways and develop "targeted therapies" based on identified causes, as in oncology." Research into new targets continues through the study of large patient cohorts. "Once newly altered genes are identified, they will become the targets for new drugs developed by industry."
 

Education and information

Micheline Misrahi-Abadou laments that "most doctors have been testing just one gene for the last 25 years, FMR1", due to a "lack of awareness and education in genetics during medical studies." To address this, in 2016, she established the "Genetics and Reproduction" institutional degree (DU), the only one of its kind in France, where 50 experts teach the applications of genetics in reproduction. She also engages with the general public "to inform them of the latest innovations in reproductive health and combat misinformation, starting with that conveyed by the media." Together with Boris Cyrulnik, she is co-editor of Nouvelles Fertilités, Nouvelles Familles Nouvelle Humanité [New Fertilities, New Families, New Humanity], (2024, Odile Jacob), which explores the genomics revolution in infertility and the upheavals it is causing in society, family models and parenting, as part of a genuine societal revolution.
 

National and international recognition and involvement

Throughout her career, Micheline Misrahi-Abadou has been Co-Director of the Institut fédératif de recherche Bicêtre (Bicêtre Federative Research Institute) and laboratory director. She is a member of several scientific advisory boards, European university councils, European academies and international evaluation bodies. She is also a recognised expert for agencies such as the French National Agency for the Safety of Medicines and Health Products (Agence nationale de sécurité du médicament) and the French Biomedicine Agency. Her research has won her several awards. Notably, she was named a winner of the 2025 Forbes-L'Oréal Awards, which celebrate women for their talent, dedication and impact.