Yvon Englert

Abstract The multicentric study regroups 128 cases of the ovarian hyperstimulation syndrome (OHSS) in in-vitro fertilization (IVF) and 256 selected controls. Values of serum oestradiol obtained from different laboratories were found to be normally distributed after ...

L'activite clinique et scientifique du Service de Gynecologie-Obstetrique s'articule sur les trois grands domaines de la specialite: ○ La gynecologie chirurgicale, dont les points forts ont ete le developpement de techniques peu invasives (laparoscopie operatoire assistee par le LASER, aujourd'hui le robot), l'etude, en collaboration avec le Service de Gastro-Enterologie Chirurgicale, de l'endometriose, pathologie frequente et delabrante, et la chirurgie oncologique. ○ L'obstetrique et la medecine foetale, ou le Service a contribue a la comprehension et a la prise en charge de maladies gravidiques, particulierement l'accouchement premature et le diabete gestationnel et a accompagne le developpement des technologies d'exploration et d'intervention sur le foetus in utero. La genetique, le diagnostic genetique prenatal, l'utilisation de la cordocentese, l'etude de l'isoimmunisation et de l'infection par le cytomegalovirus ont ete part...

The clinical activity of the preimplantation genetic diagnosis (PGD) at Erasme Hospital was carried out since September 1999 for a 47,XYY patient. Up to 31 December 2007, 79 PGD cycles were carried out (45 couples) for either chromosomal structural abnormalities (robertsonian and reciprocal translocations, pericentric inversion, deletion) (n = 41), chromosomal numerical abnormalities (47,XXY, 47,XYY, 45,X/46,XX) (n = 10), aneuploidy screening for recurrent miscarriages or multiple in vitro fertilization failures (n = 10), autosomal recessive diseases (cystic fibrosis and sickle cell anaemia) (n = 12) or X-linked disorders (n = 6). A total of 475 embryos were biopsied for genetic analysis. Unaffected embryos were transferred in 58 cycles, resulting in 22 pregnancies, including fifteen clinical pregnancies. Up to now, 9 babies were born and 3 pregnancies are still ongoing. After a learning curve, our current PGD efficiency shows a total pregnancy rate per transfer of 60.0% and an impl...

This contribution summarize ten years of in vitro fertilization of clinical work. Activity growth, improvements of results (mean fertilization rate increased from 45% to 58%, fertilization failure dropped from 18% to 7%, pregnancy chances gains 9% to reach 44% per trial) and new treatments possibilities (severe male infertility) thanks to the ICSI technic were the major characteristics of this last ten years. The original anonymous oocyte donation program with donors permutation initiated as soon as 1990 has imposed itself due to it's exceptional efficiency with a pregnancy rate of 95% per oocyte pick up on a population of 46 donors and 145 recipient cycles. Thanks to the large population studied (4028 cycles, 1071 pregnancies), the tendencies in human fecundity (impact of age) and the risks linked to multiples pregnancies could be highlighted, stressing the importance of future developments presented in the other contributions following this general presentation of results.

Les infections genitales par les virus du papillome humains (HPV) sont les infections virales sexuellement transmises, les plus communes chez les femmes en âge de procreer. Il est desormais bien etabli que l’infection persistante par les HPV classes «a haut risque» est l’un des facteurs indispensables au developpement de lesions precancereuses et cancereuses du col de l’uterus. Ces HPV semblent aussi etre impliques dans le developpement d’autres cancers de la region ano-genitale et pourraient etre egalement impliques dans les cancers de la tete et du cou. Durant cette derniere decennie, des etudes croissantes tendent a etablir un role etiologique des HPV dans les dysfonctionnements gestationnels. La detection des ADN HPV dans les placentas issus d’avortements spontanes et leur capacite exceptionnelle a se repliquer in vitro dans les cellules trophoblastiques cultivees en monocouche, ont apporte de nouvelles perspectives quant a la possibilite que le placenta pourrait constituer aussi un tropisme naturel des infections par HPV.Six jours apres la fecondation et suite a l’accolement du blastocyste a l’epithelium uterin, le trophoblaste s’engage dans des processus actifs de proliferation, d’invasion et de differenciation complexe pour la construction de l’interface physiologique indispensable aux echanges essentiels entre la mere et l’enfant ; le placenta. De facon interessante, ses proprietes sont similaires a celles de la cellule tumorale maligne. Neanmoins, ses mecanismes sont etroitement regules dans le trophoblaste, a la fois dans l’espace et le temps, assurant un developpement normal a chaque etape de la grossesse.Devant toutes ces donnees, nous avions emis l’hypothese que l’expression des proteines precoces E5, E6 et E7 d’HPV de type 16 (de haut risque), pourraient modifier le developpement des trophoblastes infectes. Les resultats obtenus durant ce travail de doctorat demontrent que la proteine virale E5, hautement hydrophobe, est cytotoxique et affecte la viabilite du trophoblaste. Cette cytotoxicite est neutralisee, et la viabilite est amelioree, lorsque les oncoproteines majeures E6 et E7 sont exprimees en presence de la proteine E5. Lorsque toutes les proteines precoces sont exprimees sous le controle de leur propre promoteur (LCR), la viabilite est favorisee. Ces observations ont ete confirmees dans les cellules cervicales egalement. Il a ete precedemment rapporte que les oncoproteines E6 et E7 affectaient l’adhesion du trophoblaste aux cellules endometriales. Dans le present travail, il a ete retrouve que la proteine E5 diminuait elle aussi l’adhesion, non seulement aux cellules endometriales, mais aussi au support de culture cellulaire. Les capacites de migration et d’invasion de la matrice extracellulaire sont augmentees par l’expression de E5 et dans une plus large proportion par l’expression de E6 et E7. Des resultats similaires ont ete obtenus lorsque toutes les proteines de la region precoces sont exprimees sous le controle de leur propre promoteur (LCR). La diminution de l’expression de la E-cadherine est consideree comme un marqueur de malignite et de mauvais pronostic pour les cancers. Nous avons demontre que l’expression de E5, E6 ou de E7, inhibait l’expression de la E-cadherine, refletant l’impact des oncoproteines du virus HPV-16 sur la diminution de l’adhesion et l’augmentation du pouvoir invasif des cellules trophoblastiques. L’investigation d’autres marqueurs de malignite et de tolerance immunitaire, l’etude de l’impact du virus HPV-6 (de bas risque) sur la migration et l’invasion des cellules trophoblastiques, et l’etude de la capacite des proteines precoces d’HPV-16 a influencer l’entree des particules virales, ont fait l’objet de resultats preliminaires, ouvrant de larges perspectives.Genital Human Papillomavirus (HPV) infections are the most common sexually transmitted infections amongst women on the age of reproduction. It is well established that persistent infection with high-risk HPVs is the necessary factor in the causation of precancerous and cancerous cervical lesions. High-risk HPVs have also been reported to be involved in the causation of head and neck cancers and other anogenital cancers. On this last decade, growing data are attempting to study the potential etiological association of HPV with gestational dysfunctions. The detection of HPV DNA in placentas resulting from spontaneous abortions and the unique ability of multiple HPV types to replicate in vitro in trophoblastic cells cultured in a monolayer system, rise new questions over the HPV tropism. Six days following fertilization and once the apposition of the blastocyst on the uterine wall takes place, the trophoblast, in a very active and complex process, starts to proliferate, invade and to differentiate in order to build a physiological interface; the placenta, from where multiple mother/foetus exchanges occur. Interestingly, the way that the trophoblast behaves is very similar to malignant tumoural cells.…

To investigate the ovarian renin-angiotensin system (RAS) during severe ovarian hyperstimulation syndrome (OHSS). Simultaneous sampling of blood and ascitic or peritoneal fluid (PF) during therapeutic paracentesis or laparoscopy. University Hospital. Twelve patients were investigated: three patients presenting severe OHSS, three patients with a spontaneous first trimester pregnancy, three normally cycling women during the early luteal phase, and three patients with ascites of nonovarian origin. Renin-like activity and angiotensin II (ANG II) immunoreactivity were measured simultaneously in the plasma and the ascites or PF. Angiotensin II immunoreactivity was much higher in the ascites or PF than in corresponding plasma during severe OHSS, first trimester pregnancy, and in the early luteal phase, while it was lower in ascites of nonovarian origin. Renin-like activity and ANG II immunoreactivity were the highest in the ascites of severe OHSS and in the PF from part of the patients with a spontaneous first trimester pregnancy. The present findings argue for the ovarian origin of the elevated renin-like activity and ANG II immunoreactivity in the ascites of severe OHSS and suggest a stimulatory role of hCG on the ovarian RAS whether during severe OHSS or first trimester spontaneous pregnancy. The vasoactive peptide ANG II may contribute to the maintenance of the ascites in severe OHSS but is probably not responsible for the formation of the ascites. The efficiency of paracentesis during severe OHSS could be explained at least partially by the removing of great amounts of ANG II from the peritoneal cavity.

Since 1999, the Erasme Hospital Fertility Clinic has carried a special programme for patients with HIV seropositivity. The philosophy of the programme is to give access to these patients in a secure environment to the same technological facilities available to any other patients. Many of these patients being native from sub-Saharan countries, they are often sickle cell disease (SCD) carriers, a common autosomal recessive disorder in these regions, and a severe affection in homozygotes. We hereby report, for the first time, the birth of a healthy sickle haemoglobin (HbS) heterozygous baby after preimplantation genetic diagnosis (PGD) for SCD in an HIV-serodiscordant couple of HbS mutation carriers with longstanding infertility. The prospective mother was 35 years old and HIV positive with an undetectable viral load under highly active antiretroviral therapy. One carrier embryo was transferred and resulted in the birth of a healthy HbS carrier baby girl. Despite stimulation difficulties, sometimes described in HIV patients, PGD represents an interesting additional technology, especially in populations where the coexistence of both diseases is frequent. PGD could even be preferred to prenatal diagnosis for couples of HbS carriers if the woman is HIV positive, as invasive prenatal samplings carry a risk of materno-foetal viral transmission.