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International audience; Objective: To provide a snapshot of the surgical management of endometriosis in French high-volume activity centers.Methods: Analysis of prospectively collected data between November 2015 and May 2017 in 21 centers with a high volume of endometriosis surgery in France. Each facility could include up to 40 patients undergoing laparoscopy for endometriosis. Data were collected before and two months after surgery.Results: 361 patients were enrolled in the study. Twenty-seven patients (7.48%) were lost to follow-up at the month 2 visit. Endometriosis stage was I-II in 33.70% of patients and III-IV in 66.30%. Uterosacral ligament resection was the most frequently performed procedure (50.97%) followed by rectal surgery (31.58%), ovarian procedures for endometrioma, procedures for ureters (21.33%) and the bladder (11.91%). Antiadhesion agents were employed in 215/361 (59.56%) patients. The median length of hospital stay after surgery was 2 (IQR 1 − 4) days. Post-operative complications were recorded in 9.34% of patients. Rectovaginal fistulae occurred in 8 patients (2.41%), pelvic abscess in 4 (1.20%) and bladder atony in 3 (0.90%). 17 patients (5.14%) required a second surgical procedure after a median time of 31 days (IQR 9 − 81). Two months after surgery, 95.09% of patients reported being satisfied or very satisfied with the surgery.Conclusion: Our study shows that surgical management of endometriosis in centers with a high volume of endometriosis surgery, mainly concerns women presenting with severe disease and deep localizations, with an overall risk of major complications inferior to 10% and a high rate of patient satisfaction.

Resume Objectif Preserver la fertilite doit aujourd’hui faire partie integrante de la prise en charge du cancer. L’objectif de notre etude est d’evaluer notre activite de preservation de la fertilite feminine au sein du CHU de Montpellier mis en place depuis 2011. Patientes et methodes etat de lieu de la pratique d’oncofertilite au CHRU de Montpellier sur 2 ans, de septembre 2011 a septembre 2013. Resultats Soixante et onze patientes ont ete adressees en consultation de preservation de la fertilite. Quarante-deux patientes (59,1 %) etaient eligibles pour la preservation de la fertilite. Vingt-deux patientes (31 %) se sont vues proposer une congelation d’ovocytes matures, 8 patientes (11,3 %) une cryoconservation de tissu ovarien, 7 patientes (9,9 %) des injections d’analogues de la GnRH, 3 patientes (4,2 %) une transposition ovarienne et seulement 2 patientes (2,8 %) une congelation embryonnaire. Sur les 42 indications de preservation de la fertilite, seulement 18 auront finalement eu lieu. Conclusion La preservation de la fertilite doit etre integree dans le programme de soins du cancer, menee par une equipe pluridisciplinaire. Il est essentiel d’ameliorer la diffusion de l’information aupres des patientes mais aussi des oncologues impliques dans la prise en charge de ces patientes.

Resume Objectifs Cette etude a pour objectif de comparer les issues de transferts d’embryons congeles (TEC) au stade blastocyste selon la technique de congelation, congelation lente versus vitrification et suivant le type de preparation endometriale. Patientes et methodes Au total, 172 TEC au stade blastocyste (J5-J6) ont ete inclus retrospectivement d’avril 2007 a decembre 2012. Les issues de TEC par technique de congelation lente (groupe 1, n = 86) ont ete comparees a celles des TEC par vitrification (groupe 2, n = 86). Plus precisement, le taux de survie apres decongelation, le taux d’implantation ainsi que les taux de grossesse clinique et evolutive ont ete compares respectivement entre ces deux groupes, apres appariement sur l’âge des patientes au moment de la congelation, sur le nombre d’embryons transferes et sur le stade embryonnaire lors du transfert. De plus, pour chacune des techniques de congelation, ces memes issues de TEC ont ete comparees en fonction du type de preparation endometriale proposee c’est-a-dire cycle naturel (groupe N) versus cycle stimule (groupe S). Resultats Les taux de survie, d’implantation et de grossesse clinique etaient significativement plus eleves pour les TEC dont les embryons etaient issus de vitrification comparativement aux TEC dont les embryons ont ete congeles par technique de congelation lente (97 % vs 85 %, p p = 0,02 ; 43 % vs 28 %, p = 0,04, respectivement). En tenant compte du nombre d’embryons transferes dans chaque groupe, le taux de grossesse multiple etait environ trois fois plus eleve dans le groupe des TEC associes a une vitrification comparativement au groupe des TEC associes a une congelation lente, mais de maniere non significative (27,3 % vs 8,3 %, NS). En revanche, les issues des tentatives de TEC n’ont pas ete significativement affectees par le type de preparation endometriale et ce quelle que soit la technique de congelation utilisee. Neanmoins, un taux de fausses couches spontanees (FCS) plus faible a ete observe dans le cas ou les embryons ont ete congeles par vitrification et transferes sur un cycle naturel (groupe N2 vs groupe S2 : 20 % vs 47 %, NS). Discussions et conclusion Notre etude confirme que le taux de survie apres decongelation de blastocyste (J5-J6) est significativement ameliore par la technique de vitrification comparativement a la congelation lente. De la meme maniere, les taux d’implantation et de grossesse clinique sont significativement augmentes en cas de TEC au stade blastocyste, lorsque ceux-ci sont issus d’une congelation par vitrification. Les resultats obtenus, grâce a la technique de vitrification, sont tres satisfaisants mais s’accompagnent d’une augmentation du taux de grossesse multiple. De plus, la realisation de TEC en cycle naturel ou stimule ne modifie pas significativement les resultats des tentatives, quelle que soit la technique de congelation utilisee. Cependant, le risque de FCS est plus limite en cas de TEC en cycle naturel et apres congelation embryonnaire par vitrification.

Resume L’endometriose pelvienne profonde est une maladie gynecologique importante et frequente, responsable de douleurs pelviennes severes. Elle est definie par la penetration du tissu endometrial ectopique sous la surface du peritoine ou a l’interieur de la paroi d’un organe pelvien, a une profondeur superieure a 5 mm. L’IRM est le meilleur examen d’imagerie pour evaluer l’extension de la maladie qui peut atteindre les compartiments posterieurs, median ou anterieur du pelvis. L’objectif de cette revue est de decrire les differentes lesions d’endometriose profonde, de souligner les points clefs qui doivent etre presents dans un compte rendu d’IRM et surtout de preciser l’impact de chacune de ces lesions sur la prise en charge des patientes avec une endometriose pelvienne profonde.

Resume Objectif Etablir si la realisation des manœuvres a membranes rompues sur deuxieme jumeau (J2) est un facteur de risque de cesarienne. Patientes et methodes Deux cent cinquante-neuf accouchements gemellaires par voie basse apres 33 semaines d’amenorrhee de 1997 a 2009 au sein d’une maternite de niveau III. Etude cas–temoins retrospective, comparant un groupe constitue de cesariennes sur J2 et un groupe temoin constitue des cinq accouchements par voie basse des grossesses gemellaires suivant le cas. Une prise en charge active de J2 etait effectuee avec un intervalle libre court entre les deux naissances. Resultats Onze cesariennes sur J2 (4,2 %) ont ete pratiquees. L’indication la plus frequente etait l’echec de la version par manœuvre interne. Le risque de cesarienne sur J2 etait plus eleve quand les membranes etaient rompues immediatement avant ou pendant la version par manœuvre interne (VMI) (OR : 25,4 IC 95 % [2,35–275,7] p Discussion et conclusion Dans notre experience, la rupture des membranes avant ou pendant la VMI est significativement associee a un risque d’echec de la manœuvre et de cesarienne sur J2. Par consequent, nous preconisons d’effectuer la VMI a membranes intactes conformement a l’accord professionnel des recommandations francaises de 2009.

The good folliculogenesis evolution is fundamental for the obtaining of a competent oocyte, able to lead to pregnancy, once fertilized. During the follicular development, the oocyte is in close contact with surrounding cumulus cells (CCs) to form a cumulus-oocyte complex. The bidirectional exchange between oocyte and contiguous CCs via gap junction communications and paracrine signaling is important for oocyte competence and CCs development. These reciprocal regulations are controlled by some key genes. Recently, it has been demonstrated that these genes are themselves regulated by short RNAs fragments (approximately 22 nucleotides), called microRNAs. The identification and the quantification in the CCs of the microRNAs regulating these genes could promote the development of non invasive tests in order to assess the oocyte quality and its ability to provide embryo with a high implantation potential. This approach could be decisive in the embryo selection to transfer and could avoid the risk of multiple pregnancies by the replacement of a single embryo.

The appreciation of endometrial receptivity is a crucial step in assisted reproductive technology as implantation failures are thought to result, in large part, from abnormal endometrial receptivity. Using emerging omics technologies, investigators have begun to define both molecular signatures and specific biomarkers of receptive endometrium. The aim of this review was to analyse the new perspectives brought to the appreciation of endometrial receptivity by transcriptomic and proteomic technologies, involving the analysis of gene- or protein-expression-profile shifts between the pre-receptive and receptive secretory stages and how they might lead to new strategies for endometrial receptivity assessments. The use of omics as molecular tools to determine the effects of stimulation protocols on endometrial gene expression and clinical outcomes has also been investigated. The appreciation of endometrial receptivity is a crucial step in assisted reproductive technology as implantation failures are thought to result, in large part, from abnormal endometrial receptivity. Using emerging omics technologies, investigators have begun to define both molecular signatures and specific biomarkers of receptive endometrium. The aim of this review is to analyse the new perspectives brought to the appreciation of endometrial receptivity by omics technologies, involving the analysis of gene- or protein-expression-profile shifts between the pre-receptive and receptive secretory stages, and how they might lead to new strategies for endometrial receptivity assessments. The use of omics during IVF procedures as molecular tools to determine the effects of stimulation protocols on endometrial gene expression and clinical outcomes has also been investigated.

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was first to focus on the knowledge of the effects of cigarette smoking on reproductive stages and particularly on implantation process and early placentation. Human clinical and experimental studies were analysed in order to find hypothesis and explanations for the effects observed. Then, our second aim was to analyse which factors could influence smoke effects. We observed that smoke compounds induce impairment of endometrial maturation, disturb angiogenesis and trophoblastic invasion. Cigarette compounds also impair uterine and endometrial vascularisation and myometrial relaxation. These effects lead to implantation failure in IVF and higher risk of miscarriage. Many factors influence the effects of cigarette smoke, as smoke behaviour, dose and duration of exposition. Sidestream is also damaging on reproductive function. Prenatal exposure leads to irreversible and deleterious effects on ovarian reserve. These observations need to be confirmed in order to improve health care in women of reproductive age.

Cigarette smoking is associated with lower fecundity rate, adverse reproductive outcomes and higher risk of IVF failure. Over the last decades, prevalence of smoking among women of reproductive age has increased. The aim of this work was to focus on the knowledge of the effects of cigarette smoking on all reproductive stages, from oocyte to embryo. For each reproductive functions human clinical and experimental studies were analysed in order to find hypothesis and explanations for effects observed. All reproductive functions are targets of smoke compounds and cigarette smoking impairs ovarian reserve, sexual steroids synthesis, Fallopian tubes functions and embryo development, leading to reduced fecundity. Some of smoke compounds were identified in ovarian tissue, in uterine fluid and in the embryo, suggesting direct toxicity.

Background Crosstalk between human trophectoderm (TE) and endometrial cells during the implantation window is a complex and not well-understood process. The aims of this study were (i) to evaluate the global gene expression profile in TE cells from Day 5 human blastocysts issued from IVF, (ii) to compare these data with the transcriptomic profile of endometrial cells in stimulated cycles for IVF and (iii) to identify potential early dialogues between maternal and embryonic cells during the implantation window. Methods Endometrial biopsies (n = 18) from normal responder patients were performed on the day of embryo transfer (Day 5 after human chorionic gonadotrophin administration). TE biopsies from five blastocysts donated for research purposes were mechanically extracted. DNA microarray analysis was carried out to identify the specific gene expression profiles and the biological pathways activated during the implantation window in endometrial and TE cells. Results Several cytokines (such as PDGFA, placenta growth factor, IGF2BP1 and IGF2BP3) were up-regulated in human TE cells, whereas some of the corresponding receptors (PDGFRA and KDR) were over-expressed in the receptive endometrium, suggesting that these molecules are involved in the early dialogue between blastocyst and maternal endometrial cells. In addition, several adhesion molecules and extracellular matrix proteins (MCAM, ITGAE and LAMA1) were also over-expressed in the TE, while others (ALCAM, CEACAM1, PECAM1, ITGB8 and LAMA2) were restricted to the receptive endometrium. Conclusion The present study shows that several growth factors, cytokines, integrins and adhesion molecules are expressed in the TE and endometrium at the time of implantation. These results could contribute to the understanding of the mechanisms involved in the early dialogue between blastocyst and endometrium during implantation. Such results should be confirmed by further studies.

Resume Objectif Evaluer la fertilite des patientes atteintes d’endometriose et traitees par cœlioscopie puis par assistance medicale a la procreation. Patientes et methodes Etude retrospective sur 79 patientes presentant une infertilite associee a une endometriose, apres traitement cœlioscopique. La fertilite a ete etudiee selon le mode d’obtention de la grossesse (spontanee ou par AMP) et selon le stade AFSr de l’endometriose. Resultats Apres cœlioscopie, 8,9 % des patientes ont eu une grossesse spontanee. Le taux cumule de patientes enceintes apres cœlioscopie puis IIU etait de 21,5 %. Enfin, apres cœlioscopie puis IIU puis FIV, 68,4 % des patientes ont obtenu une grossesse. Le delai moyen d’obtention de grossesse spontanee a ete de 460 jours, de 271 jours en IIU et de 600 jours en FIV. Parmi les stades I-II (n = 62 patientes), 11,3 % des patientes ont obtenu une grossesse spontanee apres traitement cœlioscopique. L’IIU a fait passer le taux cumule de patientes enceintes a 25,8 % et la FIV a 66,1 %. Le delai moyen d’obtention de grossesse a ete de 460 jours apres cœlioscopie, de 279 jours en IIU et de 589 jours en FIV. Parmi les stades III-IV (n = 17), le taux cumule de patientes enceintes etait de 76,4 %. Aucune grossesse spontanee n’a ete observee. 94,1 % des patientes ont beneficie d’un traitement par FIV avec un taux de patientes enceintes de 70,6 %. Le delai moyen d’obtention d’une grossesse etait de 563 jours. Conclusion Une prise en charge des patientes ayant une endometriose par cœlioscopie puis par AMP permet d’obtenir une grossesse chez plus de deux tiers d’entre elles dans un delai de moins de deux ans, et cela quel que soit le stade de la pathologie. Cette prise en charge successivement par cœlioscopie puis par AMP potentialise les chances de grossesse. Actuellement, le delai optimal de prise en charge en AMP suite a un traitement cœlioscopique reste a definir.

BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

This study aimed at evaluating parameters and results of ovarian stimulation for myotonic dystrophy type 1 (DM1) female patients undergoing preimplantation genetic diagnosis (PGD) and to assess an eventual association between genotype and ovarian reserve. A retrospective study involved all 17 DM1 patients treated in the study centre's PGD programme. The control group consisted of 22 patients treated for X-linked disorders in the same period. Comparative analysis of ovarian stimulation parameters and results was performed with bivariate and multivariate analysis. Then, among DM1 patients, a correlation between genotype (number of CTG repeats) and ovarian reserve, assessed by antral follicle count, was investigated. Comparative study showed no difference concerning the number of oocytes, embryos and pregnancy rate between the two groups. Multivariate analysis demonstrated that DM1 patients needed a significantly higher dose of gonadotrophins (+544IU, P0.001) than X-linked disorders patients and suggests a decreased ovarian sensitivity. However, with higher dose of gonadotrophins, PGD for DM1 offers good reproductive outcomes with a clinical pregnancy rate of 35.7%. Genotype was not correlated to ovarian reserve and appeared not to be helpful for the choice of the dose of gonadotrophins.

The impact of gonadotropin-releasing hormone (GnRH) agonist long compared with GnRH antagonist protocols, under in vitro fertilization conditions on endometrial receptivity, is still debated. Therefore, we compared the effect of both GnRH antagonist and agonist long protocols on the endometrial receptivity by analyzing, to our knowledge for the first time, the global gene expression profile shift during the prereceptive and receptive stages of stimulated cycles under the two GnRH analogue protocols compared with natural cycles in the same patients. For the same normal-responder patients, endometrial biopsies were collected on the day of oocyte retrieval and on the day of embryo transfer after human chorionic gonadotropin administration of a stimulated cycle with either GnRH agonist long or GnRH antagonist protocols and compared with the prereceptive and receptive stages of a natural cycle. Samples were analyzed using DNA microarrays. Gene expression profiles and biological pathways involved during the prereceptive stage to the receptive endometrial transition of stimulated and natural cycles were analyzed and compared for each patient. Both protocols affect endometrial receptivity in comparison with their natural cycle in the same patients. Major differences in endometrial chemokines and growth factors under stimulated cycles in comparison with natural cycles were observed. Such an effect has been associated with gene expression alterations of endometrial receptivity. However, the endometrial receptivity under the GnRH antagonist protocol was more similar to the natural cycle receptivity than that under the GnRH agonist protocol.

This review aims to evaluate whether severe endometriosis has an impact on the outcome of in vitro fertilisation (IVF), whether IVF is associated with specific complications in this context, whether a specific ovarian stimulation protocol is most appropriate, whether the endometrial condition progresses following ovarian stimulation, and whether endometrial cysts pose a specific problem for IVF. In patients with severe endometriosis, IVF represents an effective treatment option for infertility, as a complement to surgery. The prognostic parameters of IVF are identical to those of other patients. However, the risks related to the severity of endometriosis, particularly the risk of ovarian deficiency, need to be considered. Because of this issue, to which endometriosis-related pain often adds, IVF treatment should be initiated as early as possible, using appropriate protocols and after having fully informed the patient about the specific oocytes retrieval-related risks.

Resume Objectif Le cerclage isthmique par voie abdominale est indique dans les echecs de cerclage par voie vaginale, les pertes fœtales recurrentes du second trimestre et les conisations etendues ou delabrements cervicaux. L’approche cœlioscopique plus recemment decrite doit demontrer, outre sa faisabilite technique, son interet en termes de prevention des accidents obstetricaux. Patientes et methodes Il s’agit d’une evaluation retrospective monocentrique sur 14 cas de cerclage isthmique cœlioscopique selon la technique de Benson, realises hors grossesse entre mai 2005 et novembre 2007. Nous avons analyse les antecedents obstetricaux, les etiologies de beances cervico-isthmiques, les therapeutiques deja mises en œuvre pour leur prise en charge et le devenir de ces patientes apres cerclage. Resultats L’âge moyen des patientes est 33,5 ans. Quatre-vingt-treize pour cent d’entres elles avaient au moins un antecedent d’avortement tardif ou d’accouchement premature et 42,9 % avaient deja eu un echec de cerclage par la technique de Mac Donald. Les indications de cerclage par voie haute ont ete portees dans six cas pour antecedent d’echec de cerclage par voie vaginale et dans huit cas pour impossibilite anatomique du cerclage par voie vaginale. La duree operatoire des cerclages a ete de 45 minutes (35–60 minutes) et la duree d’hospitalisation d’un jour. Aucune complication n’est, a ce jour, survenue en per- ou postoperatoire. Sur les 14 cerclages realises, six ont abouti a une grossesse. Cinq grossesses ont ete menees a terme avec naissance d’enfants vivants. Une grossesse s’est terminee par un avortement spontane du premier trimestre. Discussion et conclusion Le cerclage isthmique par voie cœlioscopique est techniquement realisable et apporte aux patientes les avantages de la cœlioscopie. L’indication doit etre correctement posee et doit repondre aux memes criteres que le cerclage par laparotomie. L’evolution des grossesses cerclees par cette technique semble etre favorable.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 38 - N° S1 - p. F35-F42

Identification of new criteria for embryo quality is required to improve the clinical outcome of in vitro fertilization. The aim of this study was to determine the gene expression profile of cumulus cells (CC) surrounding the oocyte as biomarkers for embryo potential and to identify genes to be used as prognostic indicators of successful pregnancy. CC from single oocytes were analysed using DNA microarrays. Gene expression profiles of CC surrounding the oocyte associated with good embryonic quality and pregnancy outcome were computed. We observed that CC issued from oocytes that developed into embryos with a good morphology had differing gene expression profile according to the pregnancy outcome of the embryo. We demonstrated that the expression of BCL2L11, PCK1 and NFIB in CC is significantly correlated with embryo potential and successful pregnancy. These results were confirmed by quantitative RT-PCR. The gene expression profiling of human CC correlates with embryo potential and pregnancy outcome. BCL2L11, PCK1 and NFIB genes are proposed as biomarkers for predicting pregnancy. Our findings suggest a non-invasive approach, offering a new potential strategy for competent embryo selection. This approach should be validated in single-embryo transfer programmes.

Background Identification of new markers assessing endometrial receptivity may help in improving the clinical outcome of IVF. This study aimed at identifying genes expressed in human endometrium during the implantation window that could be used as such markers. Methods A series of normoresponder patients (n = 31) underwent endometrial biopsies (n = 62, 2 per patient) during the early secretory phase, 2 days after the LH surge (LH + 2) and the mid-secretory phase (LH + 7) of the same natural cycle that preceded a new ICSI attempt for male infertility factor. Samples were analyzed using DNA microarrays and gene expression profiles at the time of the implantation window were computed. Systems biology analysis allowed the identification of biological pathways that were over-represented in this signature. A new approach for class prediction applied to microarray experiments was then used to identify biomarkers putatively involved in endometrial receptiveness. Results Five genes expressed during the implantation window were all up-regulated in the LH + 7 samples compared with LH + 2 [laminin beta3 (P = 0.002), microfibril-associated protein 5 (P = 0.009), angiopoietin-like 1 (P = 0.005), endocrine gland-derived vascular endothelial growth factor (P = 0.049) and nuclear localized factor 2 (P = 0.007)]. Increased expression was validated by quantitative RT-PCR. Conclusions Five genes have been identified for the first time as being up-regulated during the implantation window and are proposed as new biomarkers for exploration of endometrial receptiveness. As the endometrial biopsy procedure can be performed during a natural cycle, it would be worth testing this approach as a novel strategy in patients with poor implantation after IVF or ICSI.

Apoptosis is a cell death program involved in different steps of spermatogenesis, first at puberty, at the beginning of spermatogenesis, then in adult testicles by controlling normal spermatogenesis. As a result, apoptosis deregulation can affect spermatogenesis. Many studies have provided evidence that apoptosis deregulation in germinal cells resulted in male infertility. In addition, apoptosis detection in ejaculated spermatozoa arouses a growing interest in research as a reliable marker of spermatozoon quality. The aim of this review is to summarize our knowledge on physiological apoptosis during spermatogenesis, and then analyse the possibility of using apoptotic markers as selective markers of spermatozoon quality to optimize the rate of success of in vitro fertilization.

En el 40-50% de las parejas que consultan por infertilidad se encuentra una enfermedad tubarica distal. La afectacion de la ampolla y la trompa provoca una modificacion de las relaciones tuboovaricas y una alteracion de la captura y la migracion del ovocito. En la actualidad, existen dos posibilidades terapeuticas para esta infertilidad tubarica: la cirugia reparadora mediante laparoscopia y la fecundacion in vitro. El tratamiento quirurgico consiste en una adherenciolisis, una fimbrioplastia o una neosalpingostomia, segun el tipo de afectacion tubarica. Las tasas de embarazo despues del tratamiento quirurgico reconstructivo son de alrededor del 30-40%. Es indispensable realizar una seleccion rigurosa de las pacientes a partir de los datos histerograficos y laparoscopicos para determinar las que sean candidatas a una cirugia reparadora o a una fecundacion in vitro. La valoracion de la trompa y sobre todo de la mucosa tubarica durante la laparoscopia es uno de los elementos fundamentales para tomar la decision terapeutica y en el pronostico de embarazo espontaneo. La cirugia es un complemento de la fecundacion in vitro y el objetivo consiste en combinar ambas posibilidades terapeuticas para mejorar la tasa de embarazo intrauterino.

Epidemiological evidence clearly shows that obesity contributes to menstrual disorders, infertility and poor pregnancy outcome. Clinicians face two problems: obesity-related infertility and, consequently, obesity in women using assisted reproductive technologies. Whereas weight loss constitutes the first-line therapy for the former, the same does not always apply for the latter. Much debate surrounds the relationship between overweight patients and the outcome of IVF treatment. Adjusting the dose of gonadotropins is the most characteristic feature of IVF treatment in such patients. Nevertheless, considering the poorer outcome of pregnancies in obese patients, all efforts (changes in lifestyle habits, psychological counseling, antiobesity medical therapy and, possibly, bariatric surgery) should be made to encourage weight loss before fertility treatment is begun.

Since the beginning of IVF, natural cycle In Vitro Fertilization (NC-IVF) has been largely replaced by IVF with ovarian stimulation. However, natural cycle IVF has several advantages: low cost, no risk of ovarian hyper stimulation syndrome, very low risk of multiple pregnancy. Nevertheless, natural cycle IVF is less effective with a high risk of cancellation due to premature rise of LH, and an increased risk of failed oocyte retrieval. Using GnRH antagonists in a modified natural cycle decreases the occurrence of a premature LH rise. In the context of a poor responder patient, natural IVF could theoretically yield a better quality oocyte coming from a naturally selected follicle and allow a transfer on an endometrium whose receptivity has not been distorted by controlled ovarian stimulation. However, the real place for it has yet to be defined as we lack published data. Only one randomised controlled study in poor responders showed a similar pregnancy rate to a standard protocol representing a cost-effective alternative. Available retrospective data seem to show the same trend especially in the sub group of younger patients (below 38). Natural cycle IVF is a low-risk, low-cost procedure whose interesting results should be further confirmed by large scale prospective studies.

To examine the outcome of in vitro fertilization according to the body mass index of infertile patients.Between September 2003 and May 2005, 573 patients underwent 789 in vitro fertilization cycles or ICSI because of male factor, tubal factor, and unexplained infertility were retrospectively included from our IVF database. The patients were classified in four groups: BMI20 kg/m2 (264 cycles), 20or = BMI25 (394 cycles), 25or = BMI30 (83 cycles), and BMIor = 30 (48 cycles). All patients had a long protocol for IVF with a combination of the GnRH agonist and recombinant FSH.All parameters of ovarian response were comparable except the total required r-FSH dose. This dose was statistically higher in the group of BMIor = 30 compared to the other groups (p = 0.0003). All parameters of IVF outcome were comparable, including the cancellation rate, the implantation rate, and pregnancy rates.Obese patients require a higher r-FSH dose to achieve follicular maturation than normal weight patients. Obesity does not affect negatively results of in vitro fertilization.

Resume Objectif. – Determiner les facteurs echographiques predictifs de la reponse ovarienne en FIV. Patientes et methodes. – Etude prospective de 41 patientes avec un taux de FSH normal, incluses dans le cadre d'une FIV. Le nombre de follicules antraux, le volume et la surface ovarienne ont ete mesures par une echographie endovaginale au troisieme jour du cycle chez 20 patientes, et en periode de desensibilisation chez 21 autres. Les criteres principaux d'evaluation de la reserve ovarienne sont le nombre de follicules le jour du declenchement dont le diametre est superieur ou egal a 14 mm, le nombre d'ovocytes ponctionnes et le nombre d'embryons obtenus. Resultats. – Le nombre de follicules antraux est correle de maniere significative avec le nombre de follicules ( r = 0,7 ; p r = 0,46 ; p = 0,008) et avec le nombre d'embryons ( r = 0,44 ; p = 0,01). Le volume et la surface ovariens ne sont correles de maniere significative qu'avec le nombre de follicules le jour du declenchement (respectivement r = 0,51 ; p = 0,0006 et r = 0,53 ; p = 0,0004). Discussion et conclusion. – Notre etude montre la valeur predictive du nombre de follicules antraux sur la reponse ovarienne en FIV. L'echographie a j3 du cycle ou en periode de desensibilisation est un examen facile, peu couteux et reproductible qui pourrait etre propose a chaque tentative de FIV.

Resume Les anomalies chromosomiques sont a l'origine de la majeure partie des pertes embryonnaires en periode pre- et postimplantatoire. Pour l'essentiel, elles sont issues d'erreurs de segregation chromosomique au cours de la meiose feminine, et en particulier lors de la premiere division meiotique. En consequence, l'analyse chromosomique des ovocytes matures est une source d'informations essentielles pour l'etude de la formation et de l'etiologie des anomalies chromosomiques dans l'espece humaine. Durant les 40 dernieres annees, ce domaine d'investigation n'a jamais cesse de progresser au gre des innovations technologiques. Ainsi, des etudes cytogenetiques conventionnelles et des etudes de cytogenetique moleculaire ont ete menees et ont fourni de nombreuses donnees sur l'incidence et la distribution des anomalies chromosomiques dans les gametes femelles. Toutefois, les resultats rapportes presentent d'importantes variations qui traduisent les limites inherentes a l'application de ces techniques sur les ovocytes humains. Les donnees les plus fiables rapportent des taux d'anomalies chromosomiques de 15 a 20 % dans les ovocytes humains et ont mis en evidence l'implication conjointe des mecanismes de non-disjonction chromosomique et de separation des chromatides sœurs dans la survenue des aneuploidies ovocytaires. Par ailleurs, les etudes les plus recentes fondees sur de larges echantillons d'ovocytes ou de globules polaires ont permis de confirmer l'effet de l'âge maternel sur l'incidence des anomalies chromosomiques.

OBJECTIVE: To report a child born with renal impairment following severe anhydramnios due to maternal exposure to an angiotensin II receptor type 1 (AT1) antagonist, valsartan, and hydrochlorothiazide during the first 28 weeks of pregnancy. CASE SUMMARY: A hypertensive woman treated with valsartan 80 mg/day, hydrochlorothiazide 12.5 mg/day, prazosin 10 mg/day, lysine acetylsalicylate 100 mg/day, and levothyroxine 250 μg/day became pregnant. At 28 weeks' gestational age, severe anhydramnios associated with high β2-microglobulin levels in the fetal blood cord was observed. Upon discontinuation of valsartan, fetal renal prognosis improved. In this case, using the Naranjo probability scale, the renal insufficiency of the child was probably related to valsartan. At the age of 2.5 years, the child presented with only mild chronic renal insufficiency. Growth parameters were within the normal range, and there was no evidence of developmental delay. DISCUSSION: Exposure to AT1 antagonists during the second part of pregnancy can lead to abnormalities similar to those observed after exposure to angiotensin-converting enzyme inhibitors, that is, reduced fetal kidney perfusion that may result in oligoamnios and neonatal renal insufficiency. Fourteen previous reports of maternal exposure to AT1 antagonists during this period have been published. In 6 cases, fetal or neonatal death occurred; in 2 cases, pregnancy was terminated because of complete anhydramnios or fetal abnormalities; in 1 case, renal insufficiency persisted at 8 months of age; in 2 cases, kidney function was fairly normal at birth; and in 4 cases, including the one described here, neonatal renal failure improved in the first year of life. CONCLUSIONS: AT1 antagonists should be avoided throughout pregnancy. If these agents are prescribed accidentally to a pregnant woman, monitoring of amniotic fluid volume and β2-microglobulin fetal blood levels after discontinuation of the AT1 antagonist can provide critical data for advising parents on pregnancy and fetal outcome.

Resume Les cellules souches sont des cellules indifferenciees, capables d’auto renouvellement et de differenciation en cellules filles specialisees. A cote des cellules souches embryonnaires, on distingue les cellules souches adultes, fœtales, et celles du sang de cordon ombilical. Ces cellules sont multipotentes. Les cellules souches embryonnaires germinales humaines (EG) qui sont aussi des cellules fœtales ont fait la preuve de leur pluripotence, puisqu’elles sont capables de donner des derives des trois feuillets embryonnaires primitifs. Ces dernieres cellules ont un caryotype normal, et montrent une remarquable capacite de proliferation a long terme. Les cellules souches fœtales et du sang de cordon ont deja ete utilisees dans des protocoles de therapie cellulaire de la maladie de Parkinson, des deficits immunitaires congenitaux et des hemopathies. Les applications en biologie de la reproduction concernent l’etude des mecanismes de transmission de l’empreinte genetique grâce aux cellules EG. Le gynecologue–obstetricien pourrait occuper une place centrale au cœur de la production et de l’etude des cellules souches fœtales, a partir des produits d’IVG ou lors du recueil des cellules souches du sang de cordon.

The goal for any infertile couple is to explore all reasonable attempts to achieve pregnancy. The couple with infertility resulting from tubal disease has two therapeutic options to achieve this goal: reconstructive tubal surgery and in vitro fertilization. However, the increasing demand for new techniques of assisted reproduction has called into question the value of the more established methods of treatment for tubal infertility. There are some causes of tubal infertility for which surgery has virtually no chance of success. For these situations, in vitro fertilization is clearly the only therapeutic option. For other situations, the decision-making process requires detailed discussion on the effectiveness, adverse effects and cost of the procedures. Endoscopic evaluation of the tubal mucosa is essential for the selective application of tubal surgery. The available evidence shows that tubal surgery can be as, or more, effective as in vitro fertilization for cases of filmy adhesions, mild distal tubal occlusion and proximal obstruction. It may, however, be reasonable to discuss in vitro fertilization with any couple without pregnancy 12 months after tubal surgery. In women with moderate to severe distal tubal disease, the diminishing success rates from surgery suggest that in vitro fertilization should be considered as the first line of treatment. In the case of unsuccessful reconstructive surgery, or if a hydrosalpinx is irreparably damaged, a salpingectomy prior to in vitro fertilization has to be considered. Tubal surgery has indisputable benefits for the patient if infertility is cured by the intervention. A successful tubal repair gives the patient the possibility of conceiving more than once without further treatment. It also gives the couple the psychological advantage of being able to conceive spontaneously. Probably the most pragmatic viewpoint is to consider reproductive surgery and in vitro fertilization as complementary options that are directed towards increasing the overall probability of achieving a pregnancy in the most efficient manner.

Resumen Desde sus timidos comienzos en un circulo reducido en la decada de 1970, la fecundacion in vitro ha asistido a grandes avances gracias a los cuales han nacido hasta el dia de hoy cerca de 400.000 ninos en todo el mundo. Aunque sus principios basicos no han cambiado, la aparicion de nuevos farmacos, como los productos recombinantes, junto al desarrollo de la tecnica de inyeccion intracitoplasmica de espermatozoides, representan los progresos mas importantes logrados en los ultimos anos. Los proximos desafios que debe superar la medicina de la reproduccion seran el dominio de la implantacion del embrion y la maduracion in vitro de los ovocitos. El progreso dependera de la adquisicion y el dominio de los conocimientos fundamentales sobre el embrion, el endometrio y el ovocito. Estos desafios futuros solo podran superarse si se complementan y comparten los conocimientos de las distintas subespecialidades implicadas en la medicina de la reproduccion. Tales logros permitiran ofrecer mejores posibilidades de embarazo y, al mismo tiempo, una reduccion de los riesgos asociados a la fecundacion in vitro, en especial el de las gestaciones multiples. En lo que se refiere a la ley y la etica, no debe olvidarse nunca que el unico resultado valido para las parejas esteriles tratadas con fecundacion in vitro es el nacimiento de un hijo sano.

We have developed a preimplantation genetic diagnosis (PGD) strategy for Duchenne muscular dystrophy (DMD) allowing the simultaneous amplification of four exons (6, 8, 28 and 32) of the dystrophin gene together with ZFX/ZFY genes for gender determination. Preliminary experiments were carried out on 215 single lymphocytes from male and female individuals. Amplification rates ranged from 90.2% for exon 6 to 96.7% for exons 8 and 32. At least four of the five sequences were successfully amplified in 95.8% of single cells, and sexing was possible in 98.5%. This 5-plex assay was found to be robust enough to be used in a PGD clinical procedure and was therefore applied to a family whose female partner was a heterozygous carrier of a large deletion extending from exon 21 to exon 34 of the dystrophin gene. We have thus analysed two exons located in the deleted region of the gene, two non-deleted exons used as intrasample controls, and ZFX/ZFY genes. Cleavage stage embryo biopsy followed by PCR resulted in transfer of three unaffected embryos. The advantage of the present approach is to identify and subsequently transfer unaffected male embryos in addition to female embryos, and is now applicable to all families displaying a deletion involving at least one of these exons.

International audience; Apoptotic cell death has been reported in human oocytes and preimplantation embryos under in vivo and in vitro conditions. BCL-2 family proteins comprise both anti- and pro-apoptotic members, which are likely to play a key role in controlling oocyte and early embryo survival. However, very limited data are available on their expression kinetics during human early embryonic development. Using our DNA microarray data, we analyzed the expression pattern of 21 BCL-2 family genes in human mature MII oocytes, day 3 embryos and day 5/6 blastocysts from patients who underwent in vitro fertilization (IVF). Selected genes were further validated by qRT-PCR and their subcellular localization analyzed by immunofluorescence confocal microscopy. Our results suggest a switch from oocyte-inherited BCL-2 family transcripts, such as BCL2L10, to embryo-produced transcripts after embryonic genome activation, including BIK, BCL2L11 and NOXA. Moreover, the pro-apoptotic gene BCL2L13 was constitutively expressed throughout human early embryonic development. Remarkably, day 3 embryos expressed more BCL-2 pro-apoptotic genes than mature MII oocytes and day 5/6 blastocysts, suggesting that embryos at this stage are more prone to apoptosis. This is further supported by an absence of cleaved Caspase-3 in the oocyte and its presence in the embryo. Using a drug that induces apoptosis (gambogic acid), we were able to show activated Caspase-3 in the oocyte in addition to an alteration of BCL2L13 protein localization. Similarly BCL2L13 localization was altered in degenerated oocytes. This study opens new perspectives for understanding the molecular regulation of human oocyte and pre-implantation embryo survival and death.

To evaluate the role of hyaluronic acid in the attachment of endometrial cells to mesothelium.In vitro study of adhesion of endometrial stromal and epithelial cells to mesothelial cells.University medical center.Reproductive-age women without endometriosis undergoing surgery for benign conditions.None.The effect of hyaluronidase treatment of mesothelial cells or endometrial cells on adhesion of (51)Cr labeled endometrial stromal and epithelial cells to monolayers of mesothelium was evaluated. The expression of CD44, the hyaluronate receptor, was evaluated by western blot.Hyaluronidase pretreatment of mesothelial cells decreased the binding of endometrial stromal and epithelial cells to mesothelium by 39% (P.02) and 31% (P.03), respectively. There was no effect on endometrial cell binding to mesothelial cells or to collagen IV when the endometrial cells were pretreated with hyaluronidase. CD44 expression by endometrial stromal and epithelial cells was demonstrated by western blot.This study demonstrates that mesothelial cell-associated hyaluronic acid is involved in attachment of endometrial stromal and endometrial epithelial cells to the mesothelium. We hypothesize that binding of hyaluronic acid by endometrial cells is involved in the pathogenesis of the early endometriotic lesion.

Purpose: To evaluate the impact of salpingectomy on therates of embryo implantation and pregnancy in patients withsevere, irreversible tubal factor sterility.

Purpose: Our purpose was to determine the impact of endometrial inflammation on fertility. Methods: The study population included 49 women: 5 women bearing an intrauterine device, 33 sterile patients, and 11 fertile women. Endometrial biopsies were performed between day 17 and day 21 of the cycle. Immunostaining was performed with an ABC kit. Monoclonal antibodies were CD68 for macrophages, CD3 for T lymphocytes, and B-E8 for interleukin (IL)-6; IL-1α and IL-1β were stained with polyclonal antibodies. A double immunofluorescence staining was performed to identify endometrial cells. Macrophage and lymphocyte rates were defined as the percentage of stained cells by field. Double staining was compared among macrophages, T lymphocytes, and anti-IL antibodies in each group. Results: The macrophage rate was high for women bearing an intrauterine device, intermediate for sterile patients, and low for fertile women (P = 0.03). There was a lack of double staining between activated T lymphocytes and anti–IL-6 antibody in tubal sterility and endometriosis. Endometrial macrophages were stained with anti-IL antibodies for all groups. Conclusions: Endometrial macrophages seem to be an interesting parameter for evaluating endometrial inflammation. In tubal infertility and endometriosis, the lack of expression of IL-6 in T lymphocytes could participate in impaired embryo implantation.

Objective: To evaluate the technical aspects, efficacy and safety of first-trimester multifetal pregnancy reduction in the management of multifetal pregnancies, an analysis of the international literature on first-trimester multifetal pregnancy reduction was made. Materials: Thirty-three studies were selected from an international review of the literature. Total fetal loss rate, risk of fetal loss after the procedure with the different techniques and gestational age at delivery were the main parameters studied. The Kruskal-Wallis test and Mann-Whitney test were used for statistical analysis. Results: 2,756 multifetal pregnancy reductions were performed (2,145 transabdominal, 363 transcervical, and 248 transvaginal procedures). Total fetal loss rates were different: 16.7% for the transabdominal, 24.8% for the transcervical and 10.9% for the transvaginal procedure (p = 0.03). The risk of fetal loss was 12% for the transabdominal, 20% for the transcervical, and 10% for the transvaginal approach at less 24 weeks of gestation (p = 0.04). There was no difference for the gestational age at the time of the procedure, the initial and final number of embryos, and the gestational age at delivery. Conclusion: Because the transvaginal approach seems to be the safer procedure, surgeons may opt for it. The transcervical approach has a high fetal loss rate and should be excluded.

Inin vitrofertilization cycles, both HP-hMG and rFSH gonadotropin treatments are widely used to control human follicle development. The objectives of this study are (i) to characterize and compare gene expression profiles in cumulus cells (CCs) of periovulatory follicles obtained from patients stimulated with HP-hMG or rFSH in a GnRH antagonist cycle and (ii) to examine their relationship within vitroembryo development, using Human Genome U133 Plus 2.0 microarrays. Genes that were upregulated in HP-hMG-treated CCs are involved in lipid metabolism (GM2A) and cell-to-cell interactions (GJA5). Conversely, genes upregulated in rFSH-treated CCs are implicated in cell assembly and organization (COL1A1andCOL3A1). Interestingly, some genes specific to each gonadotropin treatment (NPY1RandGM2Afor HP-hMG;GREM1andOSBPL6for rFSH) were associated with day 3 embryo quality and blastocyst grade at day 5, while others (STC2andPTX3) were related toin vitroembryo quality in both gonadotropin treatments. These genes may prove valuable as biomarkers ofin vitroembryo quality.

Knowledge of the global pattern of gene expression is important for understanding critical regulatory pathways and key biological process governing human reproduction. Genes involved with intracellular signaling, cell survival or death, pluripotency, transcription and translation, methylation and demethylation, and nuclear reprogramming are the main cellular processes that control the early embryonic development. In this chapter, we relate recent advances on the dynamic genes changes of human early embryo development and the application of DNA microarray as a new emergent technology for embryo selection. Techniques of this type may ultimately lead to noninvasive tests for oocyte or embryo quality, revealing previously hidden information concerning both oocyte and embryonic developmental competence. Increased knowledge of genes and related transcriptional networks operative during early embryonic development should lead to advances in assisted reproductive technologies and preimplantation genetic diagnosis.

Oocyte developmental competence is altered in patients with polycystic ovary syndrome (PCOS); is gene expression in cumulus cells (CCs) from mature metaphase II oocytes of patients with PCOS altered as well?Compared with CCs from non-PCOS patients, the gene expression profile of CCs isolated from mature oocytes of patients with PCOS present alterations that could explain the abnormal folliculogenesis and reduced oocyte competence in such patients.Abnormal mRNA expression of several members of the insulin-like growth factor (IGF) family in CCs from PCOS patients was previously reported. Moreover, the whole transcriptome has been investigated in cultured CCs from PCOS patients.This retrospective study included six PCOS patients diagnosed following the Rotterdam Criteria and six non-PCOS patients who all underwent ICSI for male infertility in the assisted reproduction technique (ART) Department of Montpellier University Hospital, between 2009 and 2011.CCs from PCOS and non-PCOS patients who underwent controlled ovarian stimulation (COS) were isolated mechanically before ICSI. Gene expression profiles were analysed using the microarray technology and the Significance Analysis of Microarray was applied to compare the expression profiles of CCs from PCOS and non-PCOS patients.The gene expression profile of CCs from patients with PCOS was significantly different from that of CCs from non-PCOS patients. Specifically, CCs from women with PCOS were characterized by abnormal expression of many growth factors, including members of the epidermal growth factor-like (EGFR, EREG and AREG) and IGF-like families (IGF1R, IGF2R, IGF2BP2 and IGFBP2), that are known to play a role in oocyte competence. In addition, mRNA transcripts of factors involved in steroid metabolism, such as CYP11A1, CYP1B1, CYP19A1 and CYP2B7P1, were deregulated in PCOS CCs, and this could explain the abnormal steroidogenesis observed in these women. Functional annotation of the differentially expressed genes suggests that defects in the transforming growth factor β and estrogen receptors signalling cascades may contribute to the reduced oocyte developmental competence in patients with PCOS.Owing to the strict selection criteria (similar age, weight and reasons for ART), this study included a small sample size (six cases and six controls), and thus, further investigations using a large cohort of patients are needed to confirm these results.This study opens a new perspective for understanding the pathogenesis of PCOS.This work was partially supported by a grant from the Ferring Pharmaceutical. The authors of the study have no competing interests to report.Not applicable.