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Background & Aim Mesenchymal Stromal Cells (MSCs) are involved in several clinical trials in the field of Advanced Therapeutic Medicinal Products (ATMPs) for their properties and therapeutic potential. However, the production of MSCs is currently done in multi-plates culture chambers (CellSTACK, Corning) that only allow the production of a limited number of cells and it's time consuming. This therefore represents a constraint, especially for allogeneic uses. Now, the major challenge is to increase this production capacity. The use of a bioreactor would overcome this problem. The Xpansion® bioreactor (Pall) is composed of a controller and single-use bioreactors. Similar in concept to CellSTACK, the Xpansion bioreactors are composed of stacked cell culture plates that are sold in four variations: 10, 50, 100, and 200. Although the plastic of the bioreactor plates is identical to those of the CellSTACK, the feasibility and equivalence of quality and expansion of the MSCs produced using the Xpansion bioreactor had to be demonstrated. Methods, Results & Conclusion Preliminary tests were carried out on the smallest model of the Xpansion bioreactor product line: The XP10 (10 culture plates). All experiments were performed in parallel with a CellSTACK manipulation. The tests were performed using MSCs at passage 0 (from bone marrow or adipose tissue) or raw materials. Quantitative and qualitative tests were carried out at the end of the culture. From raw material or MSCs, cell densities obtained after 6 days of culture are equivalent in both the Xpansion bioreactor and CellSTACK, demonstrating similar cell growth. The average cell expansion rates in the Xpansion (XP10) bioreactor and CellSTACK are 24.39 times and 21.69 times (n=3), respectively. The flow cytometry analysis showed that the phenotype and viability of the MSCs from the bioreactor were not altered by this culture method. Preliminary tests on the Xpansion bioreactor have demonstrated the feasibility of MSCs cell expansion without affecting the quality of the finished product compared to the current method in CellSTACK. In addition, using a bioreactor allows the production of cells in large quantities by managing only one culture chamber while reducing the risk of contamination and operation time. Additionally, using a bioreactor improves monitoring of culture parameters and scalability. Manufacturing MSCs in this bioreactor would make the graft of a larger number of patients from the same initial collection possible.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 33 - N° 6-C1 - p. 518-524

Objective To assess intrauterine levels of leukemia inhibitory factor (LIF) by uterine flushing at the time of egg retrieval and to confirm that the procedure has no detrimental effect on pregnancy rates. Design Prospective study. Setting Assisted reproductive unit of a university hospital. Patient(s) Uterine flushing was performed in 148 IVF patients. The first 100 patients were compared with a matched control group. Intervention(s) Uterine flushing at the time of egg retrieval. Main outcome measure(s) IVF-ET results, pregnancy rates, and intrauterine LIF levels. Result(s) Pregnancy rates were not different in the group of patients with (27%) or without uterine flushing (28%). Leukemia inhibitory factor was detected in 60 patients (46%). Pregnancy rates did not differ between patients' detectable LIF and those in whom LIF was undetectable. Mean levels of LIF were 30.1 ± 49.3 pg/mL and 28.6 ± 51.2 pg/mL in pregnant and nonpregnant patients respectively. Conclusion(s) The flushing procedure at the time of egg retrieval did not adversely affect pregnancy rates. Leukemia inhibitory factor was detected in 46% of patients at the time of egg retrieval, but no correlation were observed with better pregnancy rates in patients with detectable LIF. Mean LIF levels did not differ in pregnant and nonpregnant women. Access to endoluminal secretions of the endometrium during IVF-ET may represent a new research in human implantation.

Resume Objectifs. – Presenter les alternatives chirurgicales au traitement du syndrome des ovaires polykystiques (SOPK). Patientes et methodes. – Soixante et onze patientes traitees par drilling ovarien par cœlioscopie et 47 par hydrolaparoscopie. Le critere principal d’inclusion etait la resistance a six mois de traitement par citrate de clomifene chez des patientes oligo-amenorrheiques. Resultats. – Apres une revue des principaux resultats des series chirurgicales publiees de drilling ovarien, nous retrouvons 73 % de grossesse apres traitement cœlioscopique et 61 % apres hydrolaparoscopie. Discussion et conclusion. – Les resultats sur la fertilite des drillings ovariens en font une alternative aux stimulations avec insemination intra-uterine apres echec du citrate de clomifene et/ou de la metformine. Le traitement chirurgical limite le risque de grossesses multiples et de fausses couches. L’hydrolaparoscopie apparait aussi efficace que la cœlioscopie et moins morbide chez des patientes souvent obeses.

RESUME Le travail rapporte l’experience parisienne du diagnostic genetique preimplantatoire (DPI). Cinquante-neuf couples ont ete pris en charge de janvier 2000 a juillet 2001 au cours de 71 cycles. Les ovocytes recueillis ont ete insemines par injection intracytoplasmique de spermatozoide et les embryons biopsies au troisieme jour de leur developpement. L’analyse genetique a ete effectuee le jour de la biopsie et la majorite des transferts embryonnaires ont eu lieu le quatrieme jour post fecondation. Au cours des 71 cycles, 872 ovocytes ont ete recueillis dont 731 etaient compatibles avec une injection intracytoplasmique de spermatozoide. Parmi les 505 embryons obtenus, 421 ont ete biopsies et un resultat genetique a ete obtenu pour 312 (74 %) d’entre eux. Cent vingt-sept embryons ont ete transferes au cours de 58 transferts. Dix-huit grossesses biologiques et 12 cliniques ont ete obtenues (7 uniques, 4 gemellaires et une triple). Seize enfants sont nes. Le DPI prend desormais sa place parmi les choix proposes aux couples a risque de transmission d’une maladie genetique de particuliere gravite et incurable au moment du diagnostic.

Patients with a history of repeated and unexplained implantation failure after IVF-embryo transfer and a high uterine natural killer cell count during estrogen-progestin treatment may benefit from controlled natural IVF-ET.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 33 - N° 1-C2 - p. 33-35