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Study question Can we potentiate FSH activity with antibodies to improve ovarian stimulation? Summary answer IGYXOS developed a potentiating monoclonal antibody that improves FSH potency and efficacy in vitro and in vivo as demonstrated in different animal models. What is known already FSH plays a key role in reproduction. For a controlled ovarian stimulation in IVF cycles, FSH-containing preparations are injected to patients in order to obtain mature and fertilizable oocytes. However, the efficacy of these treatments is frequently limited and sometimes several attempts are needed before reaching a pregnancy and a live birth. It was previously demonstrated that breeding animals treated with gonadotropins could develop anti-gonadotropin antibodies that enhance their bioactivity instead of inhibiting it. These females had a high kidding rate and sometimes were hyperprolific. Study design, size, duration IGYXOS developed a monoclonal antibody (mAb) directed against human FSH. The mAb CF12 was selected based on its ability to increase FSH activity in vitro and in vivo in female rat. Its potentiating activity was tested on different human FSH preparations. The potentiating effect of CF12 was further investigated in ewe treated with mAb alone or FSH alone. Participants/materials, setting, methods CF12 was tested in vitro on HEK 293 cells expressing the human FSH receptor and a cell reporter system for cAMP. In vivo, the mAb was tested according to the Steelman and Pohley protocol on different human FSH preparations. Its potentiating effect was also investigated in an ovulation induction protocol on mature ewes. Main results and the role of chance In HEK 293 cells expressing the human FSH receptor, CF12 combined to FSH improved both the potency (EC50) and the efficacy (Emax) of FSH by increasing the cyclic AMP production at all tested FSH concentrations. The potentiating activity was confirmed in immature female rats treated with hCG+FSH alone or combined to mAb, twice a day, during 3 days. The animals were sacrificed the fourth day of treatment and the weight of the ovaries was compared. Ovaries weight was significantly increased in the group treated with hCG/FSH+CF12 compared to hCG/FSH only. To further analyze the effect of CF12 on ovulation induction, it was investigated in ewe as a breeding animal model. Animals were first synchronized with a progestagen and then treated either with FSH alone or with CF12 alone. The number of ovulations was investigated by endoscopy by counting corpora lutea and the progesterone secretion was measured over the luteal cycle. All females treated with CF12 ovulated (100%) by contrast 40% ovulated with FSH treatment. The ovulation rate was 1.8 fold higher in group treated with CF12 compared to FSH group. Moreover, progesterone secretion during luteal phase was increased in animals treated with CF12 suggesting a better quality of corpora lutea. Limitations, reasons for caution After several proofs of concept obtained in different animal models, the compound is currently in the humanization phase before starting the CMC process and then preclinical studies. Wider implications of the findings The potentiating antibody CF12 is a new concept. It represents an interesting strategy in reproductive health, particularly to improve the IVF outcome. CF12 is currently developed for human application by our company and could be a game changer in the field of ovarian stimulation by enhancing the efficacy of FSH. Trial registration number not applicable

This journal suppl. entitled: Abstracts of the 26th Annual Meeting of the European Society of Human Reproduction and Embryology, Rome, Italy, 27-30 June 2010

INVO procedure is a simple and effective infertility treatment that uses a new device, the INVOcell. INVO can be performed in a physician’s office or in a satellite facility of an IVF center. The INVO procedure consists of fertilization of oocyte(s) and early embryo development in the INVOcell placed into the maternal vaginal cavity for incubation. The vaginal cavity replaces the complex in vitro fertilization (IVF) laboratory. This study presents the specially designed device, INVOcell that has received CE Certification. INVOcell overcomes the disadvantages of the previously used prototype and makes the procedure simpler and reproducible. INVO is a proven procedure that has demonstrated comparable results to conventional IVF when comparative studies were performed. Over 800 cycles have been published worldwide that showed a clinical pregnancy rate of 19.6%. The INVO technology can be performed in an office setting with minor capital equipment. INVO is a simple low-cost procedure that can be available almost everywhere. INVO allows the treatment of a new population of infertile couples who could not benefit from IVF due to cost and availability. The participation of the patient in the process of fertilization and early embryo development is a psychological benefit that creates a high level of acceptance of INVO.

BACKGROUND: It is conceivable that defective embryo hatching plays a part in the mechanisms involved in the decrease of embryo implantation rates with advancing age. In an effort to test this hypothesis, we tested the effectiveness of assisted hatching (AH) in women ≥37 years of age. METHODS: We prospectively studied 103 IVF-embryo transfer patients undergoing 103 embryo transfers. All of them were ≥37 years of age and had

Resume Entre novembre 2004 et avril 2005, 229 cycles consecutifs de FIV ont ete realises a l’hopital Antoine-Beclere de Clamart. Vingt-cinq pour cent des patientes qui ont commence une stimulation ont ete annulees en cours de monitorage. Le taux d’annulation augmente avec l’âge : pour les femmes de moins de 37 ans, il est de 20 %, pour celles de 38-40 ans, il est de 45 %, et pour celles de plus de 41 ans, il est de 50 %. La majorite des annulations a eu lieu a J8 (46 % des annulations) et J10 (40 % des annulations). On s’apercoit que c’est essentiellement le nombre de follicules en croissance (et pas le nombre de follicules total) qui determine l’arret de la stimulation. Le taux moyen de FSH plasmatique est egalement significativement plus eleve chez les femmes qui ont ete annulees par rapport aux femmes qui ne l’ont pas ete. Quand on regarde le nombre d’annulations en fonction du nombre de facteurs d’annulation, on observe que plus le nombre de facteurs augmente, plus le taux d’annulation s’accroit. L’homogeneite de la cohorte folliculaire est un nouveau parametre en cours d’etude, et qui pourrait aider a predire la reponse ovarienne du cycle suivant.

Embryo transfer is an important step in the success of IVF treatment. All efforts should be made to avoid difficult embryo transfers provoking bleeding or uterine contractions. Evaluation before IVF treatment, including a trial transfer and a uterine ultrasonography, should allow one to evaluate the transfer step, anticipate problems, and thus improve treatment. An hysteroscopy can be useful for uterine cavity exploration. It is also important to remove cervical mucus before introduce the transfer catheter. It is essential to deposit embryos as gently as possible during IVF, avoiding manoeuvres that might trigger uterine contractions which could adversely affect the results of this treatment. Soft catheters perform better, and ultrasound-guidance facilitates embryo transfer. Progesterone administration starting on the day of oocyte retrieval induces a decrease in uterine contraction frequency on the day of ET (embryo transfer). Both Wallace and CDD catheters perform similarly. Trial catheterization on the day of ET could prevent most of the unanticipated procedural difficulties during the transfer.

Maisons de naissance ou accouchement medicalise avec enregistrement permanent du rythme cardiaque foetal ? Le debat est passionnant et passionne chez les accoucheurs et les sages femmes meme s'il ne concerne probablement qu'une minorite de femmes ! Rene Frydman defend avec talent une forme particuliere de maison de naissance puisque le temps de passage de la maison de naissance a la structure hospitaliere doit pour lui etre equivalent au temps de passage d'une chambre d'hospitalisation a la salle de naissance ! Avec le meme brio, Loic Marpeau expose les avantages de la surveillance continue du RCF (qui d'ailleurs est possible dans la maison de naissance defendue par Rene Frydman !). A chacun ou plutot a chaque femme de choisir dument informee (si tant est que l'accoucheur ou la sage femme arrive a donner une information complete, eclairee et sans parti pris).

Laparoscopy is the gold standard in gynecological surgery. Single-port laparoscopic surgery, has been developed in order to improve minimally invasive surgery. We analyzed single-port approach in benign gynecologic pathology and made a bibliographic research on Pubmed and Medline from January 2000 to January 2015. From what emerges from the papers taken into consideration, single-port laparoscopy can be used for salpingostomy or salpingectomy to treat tubal ectopic pregnancy, benign adnexal disease (ovarian cystectomy, salpingo-oophorectomy), and for hysterectomy. We do not have enough data for complex procedures like myomectomy or hysteropexy. Robotic single-port laparoscopy seems to be a very attractive perspective and its use in benign gynecology surgery is expanding. More and more ergonomic limitations of single-port laparoscopy are corrected by development of articulated or flexible instruments and camera. Beyond these preliminary results, more ample prospective studies with an adapted and standardized instrumentation are thus essential to highlight real profits.

Conservative and functional surgery is increasingly used in surgical oncology. Although radical surgery remains the gold standard for treatment of cervical, endometrial and ovarian cancers, conservative approaches have been developed, aiming at preserving the potential of fertility of young patients. These procedures are proposed to selected patients, depending on histological parameters and prognostic factors as well. Therefore, a multidisciplinary approach is mandatory to weight the benefits and risks of fertility-sparing surgery.

Resume But de l’etude : Evaluer les resultats du traitement hysteroscopique des myomes sous muqueux. Patientes et methode : Entre janvier 1990 et decembre 1996, 200 patientes ont eu une resection hysteroscopique de 289 fibromes. Les indications etaient : menometrorragies (n = 159), metrorragies postmenopausiques (n = 22), cause unique d’infertilite (n = 19). Chez seize patientes, infertilite et menometrorragies etaient associees. Resultats : La duree moyenne du suivi postoperatoire a ete de 33,4 mois (± 19,2). Vingt-trois patientes ont ete perdues de vue. En raison du volume des myomes, 35 patientes ont eu une resection en deux ou trois temps, et 241 electroresections ont ete pratiquees. Douze complications ont ete observees (5 %). Aucune d’entre elles n’a entraine une reintervention, un sejour en reanimation ou un deces. Les menometrorragies ont ete controlees dans 74 % des cas. Le taux de recidives hemorragiques a ete de 16,5 % et le taux de reprises chirurgicales de 13,6 %. Les facteurs predictifs d’echecs etaient la taille du myome superieure a 5 cm, le nombre de myomes intracavitaires superieur a 3, le caractere polymyomateux de l’uterus, l’hysterometrie superieure a 12 cm et les myomes de type II. Huit des 35 patientes infertiles ont obtenu une grossesse avec un taux de naissances de 2 sur 35 (5,8 %). Conclusion : La resection hysteroscopique des myomes sous muqueux est une technique sure, efficace et reproductible dans le traitement des menometrorragies. Les myomes a large composante intramurale type II et les myomes volumineux constituent les limites de la technique endoscopique.

SummaryOne of the frequently proposed mechanisms for pregnancy losses refers to uteroplacental thrombosis. However the contribution of classical thrombotic risk factors remains questionable and, if real, does not account for a large number of pregnancy losses. The aim of this study was to investigate the presence of circulating procoagulant microparticles, a new marker of cell activation already associated with various prothrombotic clinical settings. Microparticles were assessed by an original prothrombinase assay on platelet depleted plasma obtained from 74 women with a history of pregnancy loss without apparent cause and 50 controls. Patients were studied at least 2 months after the last obstetrical event and were classified into 2 groups: 49 women with at least 3 consecutive spontaneous abortions at or before the 10th postmenstrual week and 25 with at least one fetal death beyond the 10th postmenstrual week. Among the 74 patients, 41 had increased levels of circulating microparticles, 29 belonging to the group of early pregnancy loss (59%) and 12 to the group of late pregnancy loss (48%). The high prevalence of increased levels of procoagulant microparticles in both groups makes this new marker very promising for the understanding, follow up and therapeutical handling of pregnancy loss.

Objective Several studies have suggested that GnRH is instrumental in triggering the LH surge. The present studies were performed to evaluate the effect of GnRH antagonist administration in women after the beginning of the LH surge. Design In study one, six normal cycling women were given a GnRH antagonist (20 mg Nal Glu s.c.) during an unstimulated cycle. Nal-Glu was administered when the LH level was higher than 10 U/l and associated with an oestradiol (E2) level higher than 730 pmol/l. In study two, a GnRH antagonist (3 mg Cetrorelix, ASTA-Medica, Frankfurt, Germany) was administered on day 8 of an IVF-ET cycle, in 157 women. Eighteen women among this cohort received the antagonist, when their LH level was higher than 10 U/l. Results In normal volunteers (study one), Nal-Glu was administered on day 13.7 +/- 1.4 (mean +/- SD) of the cycle when the LH level was 13.7 +/- 3.5 U/l with an E2 plasma level reaching 980 +/- 131 pmol/l. Twenty-four hours after administration of the antagonist, the LH surge had been interrupted in all subjects; it was postponed in three of the women, and abolished in the remaining three. LH levels fell by 68.5%, E2 by 42% and FSH by 53.2%. In study two, LH plasma levels 24 h after the antagonist administration fell by 94%. No premature ovulation occurred in any of the patients treated. Administering the antagonist before (n = 139) or during the LH surge (n = 18) made no statistically significant difference to the results of the IVF-ET attempt. Conclusions Our results indicate that GnRH is required throughout the gonadotrophin surge in women, not only for the initiation but also for the maintenance of the LH surge. In addition, in our study, the suppression of the rise in LH, when the antagonist was given during the surge, had no detrimental impact on IVF-ET outcome. This suggests, if confirmed on a larger scale, that late follicular phase GnRH antagonist administration to prevent the LH surge in controlled ovarian hyperstimulation (COH) is a safe and useful treatment.

This study was aimed at evaluating the in vitro effects of phosphodiesterase inhibitors and beta2-adrenoceptor agonists on spontaneous contractions of human term myometrium. Rolipram, RP 73401 (3-cyclopentyloxy-N-(3,5(-dichloro-4-pyridil)-4-methoxybenzamide) and Ro 20-1724 (1-4-(3-butoxy-4-methoxybenzyl)-2-imidozolidinone) (phosphodiesterase 4 inhibitors) inhibited spontaneous myometrial contractions (Emax approximately 100%; pD2 of 6.80+/-0.28, 6.84+/-0.32 and 6.31+/-0.03, respectively). Salbutamol and formoterol were less effective (Emax=40+/-6% and 35+/-12%, respectively) than phosphodiesterase 4 inhibitors to reduce myometrial contractility. Inhibitors of phosphodiesterase 3 (milrinone and siguazodan) and 5 (zaprinast) were marginally effective. Rolipram (10-30 nM) and siguazodan (0.1 microM) potentiated the response to salbutamol (Emax=75+/-12%, 88+/-8% and 73+/-12% and pD2=6.51+/-0.20, 6.93+/-0.29 and 6.48+/-0.16, respectively). Sodium nitroprusside (pD2=6.76+/-0.29) and theophylline (pD2=5.15+/-0.22) were effective inhibitors of myometrial contractions. Chromatographic separation of phosphodiesterase isoenzymes demonstrated that phosphodiesterase 4 is predominant but other phosphodiesterase isoenzymes were also identified. In conclusion, phosphodiesterase 4 inhibitors alone or combined with beta2-adrenoceptor agonists have potential interest as tocolytic agents.

resume Le but de l'etude etait d'evaluer la combinaison sequentielle du depistage des aneuploidies fœtales par l'echographie a 11–14 semaines d'amenorrhee (SA) et les marqueurs seriques maternels a 12–14 SA et 15–18 SA. La methode a repose sur une etude prospective incluant 1 656 patientes enceintes d'un fœtus unique et inscrites avant 13 SA dans notre maternite. Mesure de la clarte nucale par echographie a 12 SA (11–14 SA). Dosage de l'alphafcetoproteine (AFP), de la βhCG libre et de la βhCG totale par methode immunoradiometrique (12–14 SA) ou immunometrique (15–18 SA). Les risques ont ete calcules et le cut-off choisi arbitrairement a 1/250, puis ajuste pour 5 % de faux positifs. Comme resultats sept aneuploidies fœtales ont ete diagnostiquees : cinq trisomies 21, une trisomie 18 et une triploidie. Trois trisomies 21 avaient des risques eleves pour les trois depistages. Une avait un risque bas selon l'echographie et l'autre selon les marqueurs seriques. Le depistage sequentiel a permis de depister les cinq trisomies 21, meme en ajustant le cut-off pour 5 % de faux positifs (1/240, 1/160, 1/250 pour l'echographie, les marqueurs seriques du 1 er et du 2 e trimestre). En conclusion, cette etude prospective montre l'interet qu'il y aurait a associer l'âge maternel, l'epaisseur de la clarte nucale et les marqueurs seriques maternels dans le calcul d'un risque global individuel. L'algorithme correspondant devra etre etabli en se basant sur une plus large population.

New gonadotrophin-releasing hormone (GnRH) antagonists, which allow suppression of luteinizing hormone (LH) surges, have recently become available. We compared in this study the results of a single administration of 3 versus 2 mg Cetrorelix in 65 patients undergoing ovarian stimulation and in-vitro fertilization (IVF). The GnRH antagonist (Cetrorelix) was non-randomly administered at a dose of 3 mg (34 patients) or 2 mg (32 patients) on day 8 of the stimulation cycle. In the case of slow follicular development, the injection was delayed until oestradiol reached 400 pg/ml. No difference was observed in the decrease in LH and in oestradiol secretion between the 3 and the 2 mg groups, but the LH secretion was suppressed for a shorter time in the 2 mg group. No LH surge was observed in the 3 mg group, while one surge (3%) and one significant rise in LH were observed in the 2 mg group. No significant difference was observed in IVF results in the two groups of patients. This study demonstrates that a single injection of 3 or 2 mg successfully prevents LH surges for at least 3 days in all the patients treated. The LH rises in the 2 mg group led us to choose the 3 mg dose as a safer dose in our single administration protocol.

To investigate the possible consequences of uterine contractions (UC) as visualized by ultrasound (US) on in-vitro fertilization (IVF)-embryo transfer outcome, we studied prospectively 209 infertile women undergoing 220 cycles of controlled ovarian stimulation. Inclusion criteria were ageor = 38 years, a morphologically normal uterus, and at least three good quality embryos transferred. Just before embryo transfer, women underwent 5 min digital recordings of the uterus using US image analysis software for UC assessment. Plasma progesterone and oestradiol concentrations were measured. Four groups were defined according to UC frequency:or = 3.0 (n = 53), 3.1-4.0 (n = 50), 4.1-5.0 (n = 43), and5.0 (n = 74) UC/min respectively. Patients, controlled ovarian hyperstimulation and embryology characteristics were comparable in all groups. A stepwise decrease in clinical and ongoing pregnancy rates as well as in implantation rates occurred from the lowest to the highest UC frequency groups (53, 36, 21; 46, 32, 20; 23, 19, 10; and 14, 11, 4%; P0.001). Plasma progesterone and UC frequency were negatively correlated (r = -0.34, P0.001). Direction of UC did not affect embryo transfer outcome. As this study was controlled strictly for confounding variables and UC were assessed objectively by a computerized system, its results indicate that high frequency UC on the day of embryo transfer hinder IVF-embryo transfer outcome, possibly by expelling embryos out of the uterine cavity. The negative correlation between UC frequency and progesterone concentrations supports the uterine relaxing properties of progesterone.

Parents of a sample of 76 same sexed pairs of twins aged 3 to 9 months completed a mailed similarity questionnaire. It included the Bonnelykke et al.'s questionnaire and a four anthropological variable scale. To improve each of these two methods, three other combined methods were carried out and results were compared with the biological zygosity diagnosis. The Bonnelykke et al.'s classification combined with anthropological scale (method 4) gave only 1.2% misclassified in the whole sample. It is concluded that zygosity diagnosis using this type of procedure to distinguish MZ and DZ pairs would be important not only for epidemiological study but also for pediatricians and parents.

Resume Malgre la frequence de la colonisation vaginale a levures, les infections systemiques severes tant maternelles que fœtales restent rares. Nous rapportons quatre cas de candidose generalisee congenitale chez de grands prematures. Leur semiologie caracteristique a permis d'en faire precocement le diagnostic. Observations. — Un diagnostic d'infection maternofœtale (IMF) a Candida albicans a ete porte chez quatre grands prematures. Dans trois cas, la grossesse s'etait developpee malgre la presence d'un sterilet. Un examen macroscopique attentif du cordon et des membranes amniotiques a permis d'orienter d'emblee la prise en charge a trois reprises. Une alveolite infectieuse severe est constamment retrouvee dans cette serie. Une hyperleucocytose superieure a 50 000 GB/mm3 avec myelemie et une proteine C reactive (CRP) serique normale ou peu elevee sont typiques du tableau biologique. L'infection est controlee indifferemment par l'administration intraveineuse d'amphotericine B ou de fluconazole; un cas d'intolerance a l'amphotericine B nous a cependant contraints a changer d'antifongique en cours de trailement. L'evolution s'est compliquee par deux fois d'une leucomalacie periventriculaire cavitaire etendue. Conclusion. — Un tableau evocaleur d'IMF a Candida chez le grand premature peut etre degage de ces quatre observations: grossesse sur sterilet, chorioamniotite et funiculite caracteristiques, hyperleucocylose superiure a 50 000 GB/mm3, alveolite infectieuse severe. Nous proposons le fluconazole de premiere intention comme alternative interessante a l'amphotericine B.

Embryo cryopreservation is routinely used in in-vitro fertilization (IVF)-embryo transfer programmes. Yet very few studies have reported the follow-up of children conceived with frozen/thawed embryos. This study was designed to follow up the total cohort of children conceived with cryopreserved embryos in A. Beclere Hospital in Clamart, France between 1986 and 1994. We were able to study 89 children, aged 1-9 years old, out of the 93 conceived during this period (lost to follow-up: 4.3%). The prematurity rate was 14.7% for the singleton and 85.7% for the twins. Half of these premature deliveries occurred during the 36th week of amenorrhea. In all, 8% of the singleton and 28.6% of the twins were small for gestational age. At the time of the study, only three children aged 1 and 2 years old were below the 10th percentile. The total malformation rate was 3.4% when two abortions performed during the study period were added to the one (short ureter) found in our study group. The medical and surgical illness as well as principal acquisitions for children

The paper presents the design, implementation and results of a microbial single-well stimulation test performed at the Diadema field in Argentina. The purpose of the test was to achieve increased production by injecting a microbial formulation and nutrients, and to gain experience with this procedure under actual field conditions. Two out of five treated wells showed excellent oil production response to the microbial stimulation. The results suggest that a microbial-enhanced waterflood could be implemented successfully at the Diadema field.

La sterilite est une preoccupation de tous les temps. Que ce soit des tests de fecondite ou des traitements de la sterilite, les idees foisonnent et des papyrus egyptiens datant de 3000 avant JC au traitement pour le moins complique d'Hippocrate, les tentatives circulent avec des connaissances tres minces en anatomie et en physiologie. Le fœtus etait considere comme porte en miniature par la femme, les garcons a droite et les filles a gauche. Aristotei, lui, propose une theorie attestant que le fœtus provient de l'union de la femme et de l'homme. Les acquis en anatomie humaine, la description des premiers follicules (1543), des spermatozoides (1677) des ovocytes (1827) permettront, en 1853, la description en detail par Newport du processus de fertilisation et des premieres divisions embryonnaires. Les premieres inseminations avec conjoint sont faites a la fin du XVIII e siecle par un Anglais, W Hunter et un Francais, MA Thouret. Abandonne par les Europeens et repris par les Americains, les inseminations avec donneur se developpent, la conservation du sperme apparait. Parallelement, au debut du XX e siecle, sont decouvertes les gonadotrophines (FSH, LH et hCG). Il faudra attendre encore une quarantaine d'annees pour concevoir un axe neuroendocrinien. En 1978, nait Louise Brown en Angleterre, premier enfant resultant d'une fecondation in vitro (FIV). En France, c'est en 1982 que nait Amandine a l'hopital Antoine-Beclere, fruit d'une collaboration entre R Frydman et J Testart.

Human interleukin for DA cells/leukaemia inhibitory factor (HILDA/LIF) is a cytokine with pleiotropic effects involved in successful murine implantation. We evaluated human uterine HILDA/LIF production by monitoring its in-vitro secretion by endometrial explant cultures obtained from individuals in either normal or pathological conditions. The cytokine secretion was standardized using the day 5 :day 1 ratio of HILDA/LIF concentration in supernatants of such cultures, hereby termed HILDA/LIF production index (HLPI). Our results confirmed that HILDA/LIF is secreted by the human endometrium as assessed by secretion at every phase of the cycle in either normal fertile women, or women bearing intrauterine devices. This was also the case for samples obtained from infertile women presenting repeated failures of embryonic implantation or unexplained primary sterility. However, the HLPI were significantly lower in those latter two groups when compared to fertile women. These results suggest an abnormal regulation of HILDA/LIF secretion in such circumstances, and the clinical implication of those data is discussed.

The aim of this study was to show the parallel evolution of the pulsatility index of the uterine artery and the one of the median thoracic artery.The study involved seven volunteer women, below 38, suffering from premature ovarian failure, who received E2 and progesterone replacement therapy. Plasma levels of E2, progesterone, follicle stimulating hormone and luteinizing hormone were measured and PI were studied and compared before treatment and on Days 13, 27 and 41.Before treatment, a high-resistance vascular for both arteries is uniformly found. The curves show with the increasing of the E2 plasma levels, a decrease in the PI of UA and MTA with a fall at Day 13. We compared the mean values in MTA and UA PI. No statistical difference between the three mean values in PI obtained at Day -1, Day 13 and Day 41 was demonstrated.The results suggest that median thoracic artery is a target organ artery. Such as the UA, the MTA vascular resistance is according to the variations of plasma levels of E2. In consideration of it rectilinear and superficial type, this led us to study this artery when we use different sorts of replacement therapy, and particularly in the oocyte donation program.

Resume La rupture prematuree des membranes avant terme est responsable de 40 % des accouchements prematures et les risques neonataux lies a la prematurite sont generalement plus importants que le risque infectieux. Cependant, le diagnostic de chorioamniotite est trop souvent tardif et alors associe a une morbidite neonatale importante. Les principales controverses resident dans (1) le suivi des patientes en externe, (2) l'amniocentese a visee bacteriologique, (3) l'utilisation des corticoides a visee maturative pulmonaire, (4) le recours a la tocolyse. La premiere de ces controverses est l'appreciation du risque infectieux. Parmi ces parametres predicteurs d'infection intra-uterine, certains ont une bonne valeur predictive (groupe 1): fievre maternelle ≥ 38°, germes retrouves dans le liquide amniotique preleve par amniocentese ou par voie basse si ce germe est un streptocoque du groupe B, un mycoplasme, un Chlamydiae ou un gonocoque. D'autres sont moins predictifs (groupe 2) : contractions uterines, CRP maternelle ≥ 20 mg/l, glycosamnie basse. Enfin certains parametres sont de peu de valeur (groupe 3): metrorragies, oligoamnios, leucocytose maternelle ≥ 20 000/dl, leucocytamnie ≥ 100/ml et un prelevement vaginal positif. Une antibiotherapie et/ou une interruption de la grossesse peut etre proposee dans une situation a haut risque. Quand le risque de detresse respiratoire neonatale semble evite, le benefice de l'expectative reste a demontrer.

Ligation of the internal iliac arteries and embolization of the uterine arteries are two techniques routinely used in the management of postpartum hemorrhage. The objective of this study was to examine the long-term consequences of these techniques on women's subsequent reproductive outcome and subsequent delivery morbidity.Retrospective study including women who underwent ligation and those who underwent embolization, for the treatment of postpartum hemorrhage. We analyzed resumption of menses, fertility, pregnancy and delivery outcome after each treatment.The study included 85 women who underwent ligation and 90 who had embolization to treat postpartum hemorrhage. No adverse event related to menses, fertility, or pregnancy outcome followed either treatment. However, the rate of recurrent hemorrhage was high: 26% after ligation and 39% after embolization. All recurrences were treated medically in the ligation group, but in the embolization group, 42% (five of 12 patients) required invasive treatment and 33% (four patients) transfusions.From the perspective of subsequent menses, fertility and pregnancy outcome, both ligation and embolization are safe procedures for the management of postpartum hemorrhage. However, our results showed a high risk of recurrent postpartum hemorrhage after both treatments. Recurrences seemed more serious after the latter.

The recent emergence of oncofertility raises the question of ovarian stimulation and its risks when performed for oocyte or/and embryo cryopreservation in a fertility preservation program. The relation between ovarian stimulation and cancer has been marked by the possible direct or indirect tumorigenic role for pituitary gonadotrophins in the tumorogenesis. Although the growth of many gonadal and extragonadal tumors is stimulated by gonadal sex hormones, whose production is regulated by gonadotrophins, there is still a lack of data to consider FSH and LH as tumor promoters. The purpose of this brief review is to present on one hand, the questions raised by the administration of exogenous gonadotrophins in cancer patients and on the other, to evaluate both experimental and clinical data about the possible relation between gonadotrophins and tumorogenesis.

Growing evidence indicates that mild ovarian stimulation for in vitro-fertilization-embryo transfer may be an interesting approach to reduce the incidence and severity of complications, the number of treatment days, cost, patient discomfort and number of patient drop-outs. However, the heterogeneity of FSH-sensitive follicles, presumably requires multiple follicular growth to improve oocyte-embryo selection. In addition, whether the acceptability probably is similar between standard ovarian stimulation and mild stimulation, per-treatment pregnancy rates with conventional stimulation is superior to mild stimulation in unselected populations. Hence, some specific indications tend to emerge such as alterations of the ovarian follicular reserve in women of less than 38 years, bad embryo qualities and implantation failure after conventional stimulation, patients with previous history of hyperstimulation syndrome or contraindications to hyperoestrogenia (estrogeno-related cancers and thromboembolic diseases). However, no randomized trials have ever been performed to compare the results of mild versus conventional stimulation in young patients and good responders. Therefore, there is insufficient scientific evidence to shift from standard stimulation to mild stimulation for all patients. Cultural standards have to be considered in the choice of the type of stimulation.

Preimplantation genetic diagnosis (PGD) is authorized in France since 1999. After 10 years, technical results are encouraging. With the development of new technologies, our team is able to diagnosis the large majority of chromosome translocations and 75 monogenic diseases. However, PGD remains limited because of the growing augmentation of demands causing an increasing delay for the first procedure of more than 18 months. Since 2006, 19 couples asked for a PGD with HLA typing. In January 2011, 11 couples have already been included in our PGD program. The birth of the first child after PGD with HLA typing offers new perspectives of treatment for these couples.

This retrospective study aimed at analyzing IVF-ET management and outcome after cancellation of a first cycle for poor response.One hundred and forty-two infertile patients were included in this observational study. After an overall analysis on the outcome of the second IVF-ET attempt, a sub-analysis was performed according to the presence or the absence of poor prognostic criteria defined as mentioned: patient age superior to 38 years old, antral follicle count (3-9 mm in diameter) inferior to 10 on cycle day 3 and day 3 serum AMH and FSH levels less than 1 ng/mL and more than 10 IU/mL, respectively. Main outcome measures were the cancellation rates, pregnancy and live birth rates.When a controlled ovarian stimulation was performed, patients with poor prognosis had higher cancellation rates (37.8% vs. 13.3%, P0.004) and lower pregnancy and live birth rates (22.2% vs. 35.0%, P0.05 and 11.1% vs. 26.1%, P0.05, respectively) as compared to good prognosis women.The relatively high cancellation rate in patients with poor prognosis raises the question of the use of IVF modified natural cycle in this group.

The ovarian hyperstimulation syndrome is a major complication of ovulation induction for in vitro fertilization, with severe morbidity and possible mortality. Whereas its pathophysiology remains ill-established, the VEGF may play a key role as well as coagulation disturbances. Risk factors for severe OHSS may be related to patients characteristics or to the management of the ovarian stimulation. Two types of OHSS are usually distinguished: the early OHSS, immediately following the ovulation triggering and a later and more severe one, occurring in case of pregnancy. As no etiologic treatment is available, the therapeutic management of OHSS should focus on its related-complications. Thrombotic complications that can occur in venous or arterial vessels represent the major risk of OHSS, possibly conducting to myocardial infarction and cerebrovascular accidents. Once the OHSS is diagnosed, prevention of thrombotic accidents remains the major issue.

Over the past two decades, major advances in diagnostic modalities and treatment have markedly improved rates of cure for adult cancers. As a consequence, the number of long-term survivors is increasing, and fertility preservation has become a major issue for young patient about to start treatment for cancer. Whether fertility preservation is a promising option, most of the technologies currently used are far from being well established or are even still experimental. Patients should be aware that no method guarantees success. Psychological and ethical impacts of fertility preservation are major concerns and should be included in the multidisciplinary approach of the patients.

La maitrise de la «reproduction humaine» entraine de formidables esperances therapeutiques mais egalement des craintes chez les chercheurs et dans l’opinion publique. Peu a peu, a l’echelle individuelle, s’enonce le souhait d’un enfant indemne de «tout probleme», un enfant parfait. Il s’agit la d’une question fondamentale qui touche a l’existence meme de l’homme, a la rencontre du hasard et de la necessite. A l’echelle collective, apparait une autre question tout aussi fondamentale : les lois du marche appliquees aux sciences du vivant ne risquent-elles pas de conduire a court ou a long terme a une commercialisation de la cellule humaine, dont on est loin de pouvoir encore evaluer toutes les consequences?

The objective is to compare the IVF procedures in modified natural cycle outcomes according to serum anti-Mullerian hormone (AMH) levels. We included in this retrospective study 342 patients undergoing their first IVF in modified natural cycle. Patients were regrouped in three groups according to their serum AMH level: group 1 was defined by patients with AMH level0.97 ng/mL (25th percentile), group 2, patients with AMH level between 0.97 ng/mL and 2.60 ng/mL (25-75th percentile), and group 3, patients with AMH level between 2.61 ng/mL and 6.99 ng/mL (75th percentile). The main outcomes were cancellation rate, embryo transfer rate and clinical pregnancy rate, ongoing pregnancy rate and implantation rate. No difference has been observed on cancellation rate, embryo transfer rate, clinical pregnancy rate and implantation rate. The ongoing pregnancy rate per IVF cycle was respectively: 12.8±3.6% for AMH inferior to 0.97 ng/mL versus 12.5±2.5% for AMH between 0.97 to 2.60 ng/mL and 13.4±4.2% for AMH between 2.61 ng/mL and 6.99 ng/mL. In conclusion, IVF in modified natural cycles procedures should be considered as an option for patients with an altered ovarian reserve defined by a serum AMH inferior to 1 ng/mL. Serum AMH level seems a quantitative marker of the ovary but not a quality factor. Serum AMH level does not seem to be a prognostic factor for ongoing pregnancy rated in IVF modified cycles.

Intra-uterine growth retardation (IUGR) is a frequent cause of consultation in antenatal care unit. The prognosis relies on the etiology: vascular, chromosomic, genetic, or infectious. Because of chronic fetal distress, hypotrophy increase morbidity, mortality and neurosensorial long term effect. Usually, infection is involved in 5 to 15% of the IUGR, mainly by Cytomegalovirus (CMV), Varicella Zoster virus, rubella, toxoplasmosis, herpes and syphilis. Maternal sera and amniotic liquid analysis make the diagnosis possible but fetal ultrasound scan is used to find other features. Most of the abnormalities are unspecific but their combination can worsen fetal prognosis. Infection should always be ruled out in the assessment of IUGR.

A 34-year-old woman consulted the day before a scheduled caesarean for dry cough. A positive rhinopharyngeal sample for PCR testing for influenza A H1N1 led to a curative oseltamivir (Tamiflu®) treatment. At delivery a direct contact between the newborn and mother lasted only few seconds. The first healthy baby boy developped dry cough with a rhinopharyngeal sample positive for A H1N1. The minimal contact between mother and child and the positive neonatal sample only four hours after birth allow to think that it is a rare case of prenatal transmission of influenza A H1N1 to the fetus.