Paris Cancer Institute: CARPEM has a strong activity in fertility preservation. This program involves 3 main units of APHP.Centre-Univeriste de Paris: Reproductive Medicine, Reproductive Biology – Centre for the Study and Conservation of Human Sperm (CECOS) and the urology units working together.

APHP.Centre Assisted Reproductive Technology center (ART) benefits from all the authorizations for practicing fertility preservation dispensed by the Health Local Agency. APHP.Centre ART center is the most important ART center dedicated to fertility preservation in the Great Paris area and at the national level. It has been ISO 9001 certified and accredited according to ISO 15189 since 2018. This program took in charges 2444 new cases of fertility preservation during the last 3 years (2016-2018). In 2017, sperm preservation activity of our team was nearly 10% of the national activity, 8.9% for oocyte vitrification, 25.1% for ovarian cortex and 38.2% for testicular tissue (in collaboration with the fertility preservation center of the Saint-Louis APHP-site for these 2 last activities). In 2018, 516 new patients benefited from sperm preservation, 178 from oocytes vitrification, 56 from testicular tissue preservation and 73 from ovarian tissue preservation. This activity is increasing every year (e.g. more than 2 fold increase for oocyte vitrification in the last two years). Patients come mainly from medical departments of APHP.Centre – Université de Paris or hospitals affiliated to Paris University as Saint-Louis hospital or Curie Institute. Some patients, essentially for children or young people and male, are also referred by other cancer centers located outside from APHP.Centre.

Almost 30 embryologists, surgeons, psychologists, midwifes and biologists are mainly dedicated to fertility preservation patients’ care.

Guidelines have been built thanks our multi-disciplinary team. They are applied and regularly discussed with the medical teams we are cooperating with.

All these activities are structured around 1 annual cancer multidisciplinary team meeting including members of the fertility preservation program. Indications for preservation, essentially in women with gynecological cancer, are discussed once a week in different meetings dedicated to ART or gynecology surgery.

A remarkable feature of is that we are able to provide a multidisciplinary network for fertility preservation, from patients counseling, medical and surgical act achievement, to patients care for using gametes or tissues (except testicular tissue) in an ART program if needed. We are collecting all the complementary strengths within a same area to ensure a medical care throughout the process (medical, surgical, cryobiology, embryology, nurse, psychology, social, …).

Physicians surgeon and biologists of this program are strongly involved in clinical and translational research. One of the major aims of our team is to create strong interactions between researchers and clinicians in order to translate basic.

Clinical & translational research

Clinical and translational research involves 8 senior researchers. This project benefits from a joint effort gathering researchers and clinical teams from: CECOS (Dr V. Barraud-Lange), laboratory of P. Fouchet, part of the Institute of cellular and molecular radiobiology (IRCM-CEA), the Urology units from hEGP (Pr N. Thiounn) and the Fertility preservation unit of Saint-Louis APHP site (Pr C. Poirot).

This research project is led by V. Barraud-Lange. The main translational research fields are about Fertility preservation and restauration techniques.

Besides these projects, we aim i) to develop new technologies allowing the restauration of male fertility from immature testicular tissue and germinal stem cells ii) to find new freezing procedures to enhance freezing efficiency for testicular and ovarian tissues. iii) to study epigenetic features that could be modified following the cryopreservation process, and in particular Zac1 expression and its epigenetic control after oocyte vitrification in a mouse model.

Immature testicular tissue cryopreservation is the single fertility preservation option in young prepubertal boys for whom spermatogenesis has not yet started. This technique is still experimental. Indeed, if pups have been obtained in primate, no fertility restauration has been described in humans from immature testicular tissue. One of our project aims to develop testicular tissue graft and germinal stem cell (GSC) transplantation as strategies of fertility restauration from immature testicular tissue. Our topics are to (a) identity phenotypic makers allowing purifying populations highly enriched in human GSC, (b) to develop methods of culture in order to amplify human GSC in vitro, (c) to devise methods of transplantation of immature testicular tissue or of amplified GSC suspension in order to restore an endogenous spermatogenesis.

The techniques of cryopreservation of germinal tissue should also be improved in order to ensure a high survival rate of cells after tissue thawing. We collaborate with Pr A. Pelé (INSERM U698, Paris XIII University) who has developed a new polymer that could be used for human tissue cryopreservation, CryoOgel (patent registration ongoing). This new polymer is currently tested for its application on ovarian cortex freezing (co-direction of a PhD thesis, Pr C. Patrat).

Lastly, consequences of oocyte cryopreservation on early conceptus are also studied. We are particularly interested in studying transcriptome and its epigenetic control in mouse pre implantation embryos conceived after in vitro fertilization from vitrified oocytes (Dr C. Chalas, Pr C. Patrat, M2-student).

The Fertility Preservation Program integrates 8 interns and 10 fellows each year.

Medical and surgical teams are widely involved in the university teaching of fertility preservation in University of Paris and in several national teaching degrees/master’s degrees in the field of procreation and oncology, as the DU Procreation and Cancer organized by Pr C. Poirot.

The Medical and surgical teams are in charge of a national teaching program “Diplome Universitaire de Gynecologie de l’infertilité et AMP” with a specific session on fertility preservation as a part of a Continuing Medical Education (DPC) to provide continuing medical education for physicians.

This course addresses the needs of practicing scientists, gynecologists, reproductive endocrinologists, residents, and fellows who wish to review and update their knowledge in this fertility preservation.

Based on our skillness we would like to develop immature testicular tissue graft and germinal stem cells transplantation:

• To go further in the characterization of the human germinal stem cells and in the understanding of the mechanisms regulating their functions.
• To use human GSC and immature testicular tissue in clinical research program (PHRC) of regenerative medicine.

The selected 10 following publications highlighted the strong collaboration between physicians and researchers:

1. Gille AS, Lapoujade C, Wolf JP, Fouchet P, Barraud-Lange V Contribution of single-cell transcriptomics to the characterization of human spermatogonial stem cells: towards an application in male fertility regenerative medicine? Int J Mol Sc (accepted under minor revisions)
2. Poirot C, Fortin A, Lacorte JM, Akakpo JP, Genestie C, Vernant JP, Brice P, Morice P, Leblanc T, Gabarre J, Delmer A, Badachi Y, Drouineaud V, Gouy S, Chalas C, Egels S, Dhédin N, Touraine P, Dommergues M, Lebègue G, Wolf JP, Capron F, Lefebvre G, Boissel N; CAROLéLISA Cooperative Group (2019) Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation. Hum Reprod. 34:1083-1094.
3. Poirot C, Brugieres L, Yakouben K, Prades-Borio M, Marzouk F, de Lambert G, Pacquement H, Bernaudin F, Neven B, Paye-Jaouen A, Pondarre C, Dhedin N, Drouineaud V, Chalas C, Martelli H, Michon J, Minard V, Lezeau H, Doz F, Sarnacki S, Philippe-Chomette P, Dufour C, Laurence V, Baruchel A, Wolf JP, Boissel N, Valteau-Couanet D, Dalle JH. (2019) Ovarian tissue cryopreservation for fertility preservation in 418 girls and adolescents up to 15 years of age facing highly gonadotoxic treatment. Twenty years of experience at a single center. Acta Obstet Gynecol Scand. 98:630-637.
4. Poirot C, Fortin A, Dhédin N, Brice P, Socié G, Lacorte JM, Akakpo JP, Genestie C, Vernant JP, Leblanc T, Gabarre J, Delmer A, Badachi Y, Drouineaud V, Chalas C, Egels S, Touraine P, Dommergues M, Lebègue G, Wolf JP, Capron F, Lefebvre G, Boissel N. (2019) Post-transplant outcome of ovarian tissue cryopreserved after chemotherapy in hematologic malignancies. Haematologica. 104:e360-e363.
5. Pereira J, Ferraretto X, Patrat C, Meddahi-Pellé A. (2019) Dextran-Based Hydrogel as a New Tool for BALB/c 3T3 Cell Cryopreservation Without Dimethyl Sulfoxide. Biopreserv Biobank. 17:2-10.
6. Sallem A, Shore J, Ray-Coquard I, Ferreux L, Bourdon M, Maignien C, Patrat C, Wolf JP, Pocate-Cheriet K. (2018) Fertility preservation in women with cancer: a national study about French oncologists awareness, experience, and feelings. J Assist Reprod Genet. 35:1843-1850.
7. Walschaerts M, Bujan L, Chouquet C, Rossi V, Juillard JC, Thonneau P; Fédération Française des CECOS. (2018) Sperm cryopreservation incidence in men with testicular cancer: towards a stabilization in testicular cancer incidence? Results from the CECOS network. Basic Clin Androl., 3;28:11.
8. Berthaut I, Bachir D, Kotti S, Chalas C, Stankovic K, Eustache F, Ravel C, Habibi A, Brailly-Tabard S, Lévy-Dutel L, Bleibtreu A, Simon T, Galactéros F, Lionnet F, Mandelbaum J. (2017) Adverse effect of hydroxyurea on spermatogenesis in patients with sickle cell anemia after 6 months of treatment. Blood. 130:2354-2356.
9. Daudin M, Rives N, Walschaerts M, Drouineaud V, Szerman E, Koscinski I, Eustache F, Saïas-Magnan J, Papaxanthos-Roche A, Cabry-Goubet R, Brugnon F, Le Lannou D, Barthélémy C, Rigot JM, Fréour T, Berthaut I, Giscard d’Estaing S, Touati F, Mélin-Blocquaux MC, Blagosklonov O, Thomas C, Benhamed M, Schmitt F, Kunstmann JM, Thonneau P, Bujan L. (2015) Sperm cryopreservation in adolescents and young adults with cancer: results of the French national sperm banking network (CECOS). Fertil Steril. 103:478-86.e1.
10. Firlej V, Barraud-Lange V, Fouchet P. (2012) Stem cell therapy for male infertility takes a step forward. Cell Stem Cell. 11:585-6.

Annex 1:  Main indicators of clinical activities

If you are interested by this program and want to candidate to a PhD, post doctoral position, contact the leader

Dr. Catherine Patrat