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Guidelines for adequate gestational weight gain were proposed in 2009 by the Institute of Medicine. In case of a BMI30kg/m

Study question Does artificial shrinkage (AS) of blastocoelic cavity (BC) prior to fresh elective single blastocyst transfer (SBET) increase ongoing pregnancy rate? Summary answer Ongoing pregnancy rates were similar with or without AS of blastocoelic cavity. AS does not seem to provide benefit before fresh blastocyst transfer. What is known already AS of the vitrified blastocysts enhances success rate in frozen embryo transfer cycles. In vitro cultured embryos suffer changes in temperature, pH and osmotic pressure. Moreover, manipulations such as pipetting, fertilization, microscopic observations and changes of dishes can induce oxidative stress and apoptosis. The presence of cell free DNA (cfDNA) in blastocyst fluids could be the consequence of its release from dead cells. The quantity of cfDNA in blastocyst fluids could possibly be related to the rate of cell death. It is thus interesting to estimate whether AS of BC could improve the implantation rate in cycles with fresh blastocyst transfer. Study design, size, duration Prospective, randomized, double blind controlled study. From May 20th 2018 to June 30th 2021, 150 couples elected for fresh SBET were included in the study and were randomly selected as “AS +” group (n = 100), where AS of blastocoel was performed by laser pulse before fresh blastocyst transfer, and “AS -” group (n = 50), where fresh blastocysts were transferred without any additional intervention. Participants/materials, setting, methods On day 5 after fertilization, one blastocyst with a grade of expansion B3, B4, B5 or B6 and type A or B quality trophectoderm (Gardner and Schoolcraft classification, 1999) was selected for transfer. After replacement, the droplet that contained the embryo from day 3 was collected for cfDNA level quantification. Ongoing pregnancy rate was determined by the visualization of a gestational sac with a foetal heartbeat 6 weeks later and cfDNA was assessed by ALU-qPCR. Main results and the role of chance The two groups were similar for age, BMI, infertility duration and cause, stimulation characteristics and embryological parameters. The global ongoing pregnancy rate per transfer after SBET was 49.7 %. The pregnancy rate in the AS + group was slightly higher than in the control group but not significantly (respectively 50.00 % and 48,9 %, p = 0,91). cfDNA median value in the AS+ group was comparable to the control group (0.493 (0.219; 0.915) mg/ml and 0.595 (0.271; 1.129) mg/ml respectively (p = 0.45)). No link was found between cfDNA rate and clinical pregnancy rate. Limitations, reasons for caution Patients included in the study are still followed to evaluate the impact of AS on live birth rate, wastage rate, obstetrical and neonatal complications. cfDNA rate was evaluated in spent culture media and not by blastocentesis, which could provide a more accurate quantification. Wider implications of the findings To our knowledge, this is the first prospective randomized controlled study assessing the benefit of AS of BC before fresh blastocyst transfer. The inclusion of live birth rate is crucial to ascertain the interest of this technique and more studies are needed to improve the use of cfDNA in routine. Trial registration number NCT02988544

Study question Does ovarian response to controlled ovarian hyperstimulation (COH) is altered in female affected by DM1 ? Summary answer Ovarian response to COH is not altered in female affected by DM1 as compared to partners of affected males What is known already Myotonic dystrophy type 1 is the most common adult muscular dystrophy caused by a CTG trinucleotide repeat expansion which may expand across generation. As this pathology presents an autosomal dominant inheritance, PGT may be an option to achieve a pregnancy with healthy baby. There are conflicting reports about response to COH for affected female. Moreover, few data are available concerning the chance to have a healthy baby after PGT for couple with one member affected by DM1 Study design, size, duration The present study is a retrospective observational study carried out from January 2006 through January 2020. This multicentric study was conducted in all the five centers performing PGT-M in France. Participants/materials, setting, methods A total of 229 couples started at least one COH cycle for the PGT procedure. The patient carrying the mutation was the female for 178 couples and the male for the 51 others. Overall, 648 COH cycles started and 560 oocytes retrieval for subsequent PGT were performed (430 for affected female and 130 for affected male). Parameters of ovarian response and PGT outcomes were compared according to the member affected by DM1. Main results and the role of chance Age and BMI at the first COH cycle were not significantly different between both group but female carried mutation presented lower AMH level than partner of affected male. The starting and total doses of gonadotrophin were significantly higher for mutated females. The number of retrieved and mature oocytes per cycle were not statistically different (12 [8–16] versus 11 [8–16] retrieved oocytes, p = 0.63 and 9 [6–13] versus 9 [6-13] mature oocytes, p = 0.73, respectively). In both group, more than 70% of oocyte retrieval led to embryo biopsy. The proportion of started cycle allowing the obtention of at least one healthy embryo was significantly lower when the female was affected with DM1 (58.6% vs 70.4%, p = 0.012). In the female affected group, 49.7% of the cycles with oocytes retrieval lead to a fresh embryo transfer and a subsequent live birth rate per transfer of 21.4%. These results were not statistically different from the couple with affected male (58.5% of cycles with fresh embryo transfer (p = 0.08) and 23.6% live birth rate per transfer). Overall, after fresh or frozen embryo transfer, 30.8% of females with DM1and 41.2% of parter of affected males had at least one live birth from PGT. Limitations, reasons for caution This a retrospective study included patients who were selected ovarian reserve parameters before PGT process. Moreover, the large time of inclusion may influence our conclusion. Wider implications of the findings Information provided herein extends knowledge about the current state of COH for DM1 affected female. Moreover, PGT results presented here allow to provide patients with proposer counseling before starting PGT process. Trial registration number CEROG-2020-GYN-0603

Resume Objectifs Cinq a 7 % des cancers du sein touchent les femmes de moins de 40 ans. Les progres therapeutiques permettent d’ameliorer la survie de ces patientes, souvent au detriment de leur fertilite. L’objectif de cette etude est d’evaluer l’activite d’oncofertilite et le devenir des femmes jeunes atteintes d’un cancer du sein prises en charge au CHRU de Montpellier. Methodes Il s’agit d’une etude retrospective incluant toutes les femmes âgees de 18 a 43 ans presentant un cancer du sein adressees en consultation d’oncofertilite au CHRU de Montpellier entre juillet 2011 et decembre 2018. Resultats Un total de 190 patientes etaient eligibles, trois ont refuse de participer a l’etude, soit 187 patientes incluses. On estime que 33 % des patientes jeunes atteintes d’un cancer sein candidates pour la preservation de la fertilite ont pu beneficier d’une consultation d’oncofertite dans notre region. Parmi ces 187 patientes, 58 (31 %) ont beneficie d’une stimulation ovarienne en vue d’une vitrification ovocytaire ou embryonnaire, elles etaient significativement plus jeunes : 32,9 vs 34,6 ans (p = 0,01) et avaient moins de ganglions envahis. Au total 66 cycles ont ete realises et ont permis de vitrifier en moyenne 11,4 ovocytes et 3 embryons par patiente. Le taux de reutilisation etait de 3 % et 91 % des grossesses observees en post cancer etaient spontanees. Conclusion Le reseau de soin en oncofertilite semble operationnel au niveau regional. Le maintien de la sensibilisation des professionnels de sante et la creation d’un registre regional permettraient d’ameliorer notre suivi a long terme.

This review intends to introduce the changes of the new Bioethics law in the reproductive field and its application in French ART centers.The review details the main provisions of the Bioethics Law of August 2nd 2021 as well as the three decrees published since: the first one on September 29th 2021, which specifies in particular the age conditions to benefit from ART and self-preservation of one's gametes; another decree on December 31st, 2021, to set the terms and conditions for gamete self-preservation activities for non-medical reasons and the last decree on April 14th 2022, relating to the allocation of donated gametes and embryo donation.Since the law of August 2nd, 2021, access conditions to assisted reproductive technology (ART) have evolved in France. Previously based on pathological infertility or the risk of transmission of a serious disease, ART is now intended to respond to the parental project of a couple formed by a man and a woman, two women or an unmarried woman. With the widening of access conditions, the use of gamete donation will likely increase. The upcoming raise of children born from gamete donation has led the legislator to question their right to access their origin. From September 1st 2022, adults born from gamete donation will be able to request a special administrative authority in order to access the donor's non identifying data (age, physical characteristics, family and professional situation, motivation for the donation…) and/or the donor's identity. Moreover, the new bioethics law opens up the possibility of autologous gamete cryopreservation without medical reasons, under specific age conditions, in order to carry out an assisted reproduction technique later. If gametes are not used, autologous gamete preservation could also allow an increase in gamete donation. However, the modification of gamete donation conditions could suggest a short term decrease in donors' number. Finally, the new bioethics law further opens up research on human embryos and embryonic stem cells.The arrangements introduced by the Bioethics Law promulgated on August 2nd, 2021 represent a major revolution in the field of Reproductive Medicine and are expected to transform the practices of reproductive biology centers and CECOS in France.

The aim of this review is to update data concerning the impact of HLA-C KIR system on placental disorders and assess the involvement on ART clinical outcomes.Ensuring the maintenance of human pregnancy requires the set up of immunological tolerance to prevent foetus rejection. This phenomenon involves different actors of the immune system: among them, uterine NK cells (uNK) hold specific KIR (killer-cell immunoglobulin-like) receptors linking to HLA molecules on the surface of trophoblastic cells at implantation. Many studies provided evidence that the specific interaction between maternal KIR and foetal HLA-C could influence the process of placentation; according to the KIR haplotype and the type of HLA-C, the interaction could be detrimental for placental function. We reviewed the latest data available regarding HLA-C KIR interactions and ART outcomes.The available results highlight a significant increase of preeclampsia risk and recurrent miscarriages when the maternal inhibitory haplotype KIR AA is present, this risk is all the more enhanced when the interaction occurs with foetal HLA-C2. Recent data suggest the consequences of this detrimental interaction in case of DET (double embryo transfer) or use of donor's oocytes in ART practice. On the other hand, maternal KIR AB or BB haplotypes haven't been related to an additional obstetrical risk, as well as the foetal HLA-C1 homozygous allotype.Despite the existence of many confoundings in current literature on the subject, interaction between maternal KIR and foetal HLA-C represent a promising target lead to broaden the spectrum of placental defects etiologies, especially in the reproductive health area.

Resume Objectif Comparer l’issue des transferts d’embryons congeles (TEC) realises lors d’un cycle naturel en fonction de l’administration ou non d’hCG recombinante (r-hCG) pour declencher l’ovulation. Methodes Cette etude retrospective a inclus l’ensemble des patientes prises en charge pour un TEC en cycle naturel sur une periode de 1 an. Les patientes monitorees jusqu’a la detection d’un pic de LH formaient le groupe A (n = 38), les patientes ayant recu une injection de r-hCG afin de declencher artificiellement l’ovulation constituaient dans le groupe B (n = 43). Tous les embryons avaient ete conserves par vitrification. Aucun soutien de la phase luteale n’avait ete mis en place. Nous avons compare l’issue des TEC entre les 2 groupes. Resultats Apres verification de la comparabilite des 2 groupes, il n’existe pas de difference significative pour les taux d’implantation, de grossesse clinique et de naissance vivante (31 % vs 45 %, 32 % vs 51 % et 21 % vs 32 % respectivement pour les groupe A et B). Le nombre de monitorage etait significativement plus faible dans le groupe B (1,9 ± 0,8 versus 2,5 ± 1, p = 0,006) Conclusion Bien qu’aucun consensus ne soit encore etabli, le cycle naturel semble aujourd’hui s’imposer chez les patientes normo-ovulantes mais le mode de declenchement de l’ovulation reste debattu. Dans notre etude, le declenchement par r-hCG, realise en presence de criteres stricts, semble offrir de bons resultats tout en reduisant les contraintes et le cout du protocole.

Resume Objectifs La prise en charge des patientes mauvaises repondeuses reste aujourd’hui un defi therapeutique que les equipes cliniques et biologiques d’assistance medicale a la procreation doivent relever. Les criteres de Bologne, etablis lors du consensus de l’ESHRE (2011), ont propose de standardiser la definition de mauvaise repondeuse afin d’uniformiser les pratiques. Le present travail dresse un etat des lieux des connaissances actuelles concernant les differentes solutions therapeutiques. Methodes Cette mise a jour des donnees actuelles concernant les mauvaises repondeuses a ete realisee a l’aide du moteur de recherche PubMed d’octobre 2000 a juin 2016. Resultats Il n’y a pas a ce jour de protocole ideal pour les patientes mauvaises repondeuses meme si le protocole antagoniste semble avoir la preference des cliniciens et des patientes, probablement en rapport avec une meilleure tolerance, une reduction de la consommation de gonadotrophines et de la duree de stimulation. Il semblerait qu’il n’y ait aucun interet a augmenter les doses de gonadotrophines au-dela de 300 UI/jour et qu’il n’existe pas de superiorite d’une gonadotrophine par rapport a une autre. A ce jour, il n’y a pas de preuve suffisante pour recommander l’utilisation de traitements adjuvants. Seule la DHEA semble apporter un benefice en termes de qualite embryonnaire et de naissances vivantes mais des etudes prospectives complementaires sont necessaires. Conclusion De nouvelles strategies, tel que le « banking ovocytaire » ou la double stimulation sur un meme cycle, offrent aujourd’hui de nouvelles perspectives pour la prise en charge des mauvaises repondeuses.

Five to 7% of breast cancers affect women under 40 years old. The survival of these patients has been improved thanks to therapeutic advances, often to the detriment of their fertility. The objective of this study is to evaluate the activity of oncofertility and the future of young women with breast cancer managed at the Montpellier University Hospital.This is a retrospective study including women aged from 18 to 43 years-old diagnosed with breast cancer and referred in oncofertility consultation at the Montpellier University Hospital between July 2011 and December 2018.190 patients were eligible, three refused to participate to the study, hence 187 patients were included. We estimate that only 33% of young breast cancer patients potentially eligible for fertility preservation (FP) benefited from an oncofertility consultation in our region. Of these 187 patients, 58 (31%) underwent ovarian stimulation for oocyte or embryo vitrification. They were significantly younger: 32.9 vs 34.6 years old (P=0.01) and had fewer invaded lymph nodes. A total of 66 cycles were achieved and 11.4 oocytes or 3 embryos were vitrified per patient. The reuse rate was 3.6% with 91% of post cancer pregnancies being spontaneous.The oncofertility care network seems effective at the regional level. Enhancing health professionals' awareness and creating a regional register could improve our long-term follow-up.

Introduction Le diagnostic pre-implantatoire (DPI) permet d’analyser le contenu genetique d’un embryon humain obtenu par fecondation in vitro (FIV). Cette technique presente l’avantage majeur de pouvoir proposer a un couple presentant un risque eleve de transmettre une maladie genetique grave et incurable au moment du diagnostic, la caracterisation de la mutation ou du desequilibre chromosomique provenant de l’affection dont il est porteur, avant l’implantation des embryons. Une analyse cout-efficacite a ete menee (etude observationnelle financee via un appel d’offre DGOS STIC) : les resultats montrent que la strategie avec DPI est largement dominante et devrait etre adoptee. D’apres les recommandations des societes savantes, l’analyse d’impact budgetaire (AIB) doit completer une evaluation economique de type cout-efficacite ou cout-utilite : la question de l’accessibilite suivant logiquement celle de l’efficience. L’objectif poursuivi par une telle analyse est d’estimer les consequences financieres, a court ou moyen terme de la mise en place d’une strategie de sante sur le budget du payeur. Methodes La perspective retenue est celle de l’Assurance maladie obligatoire dont le budget pluriannuel sera affecte par la generalisation de la strategie etudiee. L’horizon correspond a la duree de prise en charge d’un couple dans le parcours DPI avec pour terme l’accouchement le cas echeant. La methodologie consiste a comparer le cout de la strategie evaluee avec celle de la strategie actuelle. Pour y parvenir, il est necessaire d’identifier et de definir les populations d’interet que sont la population cible (population eligible) et la population rejointe (population effectivement traitee). L’estimation de ces populations est une etape cruciale : une grande rigueur doit y etre consacree et plusieurs hypotheses sont posees. Ce travail fastidieux est gage de la pertinence de la taille des populations estimees. La problematique dans l’analyse ici menee reside dans la generalisation de la pratique du DPI (car deja repandue dans la pratique courante) et le cout qu’elle engendre. Des lors, nous proposons une AIB comparant le scenario 1 correspondant a la prise en consideration de la contrainte d’un nombre limite de DPI realisables par an et le scenario 2 correspondant a la situation dans laquelle aucune contrainte ne porte sur le nombre de DPI realisables annuellement. Une fois ces populations estimees, les ressources financieres des deux strategies peuvent etre evaluees a l’echelle populationnelle. Resultats Les donnees de couts de prise en charge estimees pour l’etude cout-efficacite, auxquelles nous avons applique de nouvelles modalites en lien avec l’AIB, sont utilisees. A partir de celles-ci, un cout de prise en charge par annee du DPI a ete deduit. Le scenario 1 est moins couteux que le scenario 2 : le differentiel maximum entre les deux scenarios sur un an est de l’ordre de 11 millions d’euros et de 33 millions d’euros sur trois ans. Lorsque l’on s’interesse aux evenements medicaux (fausse couche spontanee precoce, IMG, diagnostic prenatal et avortement spontane tardif) et aux couts evites, on constate que la prise en charge de toute la patientele cible permet d’economiser la somme de 5 025 112 € sur trois ans. Conclusion L’ensemble des parametres impactant les depenses et l’organisation de la prise en charge du DPI ont ainsi ete mis en avant. Il revient desormais au decideur d’orienter son choix, un choix eclaire des arguments avances dans cette analyse.

Introduction L’incidence des translocations chromosomiques equilibrees dans la population generale est de 0,16 % et une anomalie de structure chromosomique est mise en evidence au cours d’un bilan de fausses couches a repetition dans 5 a 10 % des cas. Un desequilibre de la translocation peut egalement engendrer une formule chromosomique viable chez le fœtus. De fait, cette anomalie de structure est parfois mise en evidence sur signes echographiques et sera alors suivi d’une IMG. Parfois, c’est suite a la naissance d’un enfant avec retard mental qu’est pose retrospectivement le diagnostic chez l’un des parents. Le diagnostic pre-implantatoire (DPI) permet d’eviter ces risques. Il est realise sur un embryon biopsie au 3e jour apres une procedure de FIV. Il permet de transferer uniquement les embryons sains. Cette technologie est couteuse, autorisee en France depuis 2000, et cinq centres seulement sont habilites. Cette etude propose d’evaluer l’efficience de la strategie de prise en charge incluant le DPI et de la comparer a la prise en charge sans DPI. Methodes Une etude observationnelle financee via un appel d’offre DGOS STIC a ete proposee. Pour des raisons ethiques, il n’a pas ete possible de randomiser les couples. Ainsi, les donnees du parcours incluant le DPI ont ete observees et le parcours sans DPI a ete obtenu via l’interrogation des bases de donnees nationales et avis d’experts le cas echeant. Le ratio cout-efficacite incremental d’un enfant vivant, de phenotype et de formule chromosomique normaux est propose. Le point de vue retenu est celui de l’AMO (Assurance maladie obligatoire) et de la collectivite. L’horizon temporel est l’accouchement et les couts directs ont ete recueillis. La methodologie des arbres de decision est retenue pour cette analyse. Le cout et l’efficacite moyenne sont estimes via les simulations de Monte-Carlo. Une analyse de sensibilite est proposee afin d’evaluer la robustesse des resultats. Resultats Au total, 376 cycles de 191 couples ont ete analyses. Le taux d’enfants nes sans anomalie est de 76,7 % par grossesse versus 3,1 % pour les couples ne beneficiant pas de DPI. La majeure partie de la difference est expliquee par un fort taux de fausse couche dans le groupe sans DPI (70 % versus 22 %). Dix mille trajectoires ont ete simulees. Le cout moyen de la prise en charge pour obtenir une grossesse du point de vue AMO est de 32 481 € [IC MC 95 % : 32 180–32 738] versus 1028 € [IC MC 95 % : 840–1228] dans le bras sans DPI. Le ratio cout-incremental est de 42 947 € [38 060–49 998] par enfant supplementaire ne vivant et normal. L’analyse de sensibilite et le graphique de Tornado, montre une robustesse des resultats. Le point de vue collectif conduit a un ratio de 49 730 €. Conclusion La strategie DPI est dominante. En effet, on obtient un ratio cout-efficacite non pas pour une unite de vie supplementaire comme cela est fait habituellement, mais pour une vie supplementaire en plein etat de sante a la naissance. Le ratio obtenu est largement en deca du seuil de 50 000 € par annee de vie gagnee. Cette strategie permet d’optimiser les ressources allouees au systeme de sante, notamment lorsque l’on considere le cout de la prise en charge des patients atteints sur une vie, mais offre egalement a ces couples une prise en charge medicale sans qu’ils aient a se decider face au dilemme d’une possible interruption de grossesse ou de la garde d’un enfant porteur d’anomalie genetique.

Finding an efficient treatment for poor responders still poses a tremendous challenge for assisted reproductive technology. In 2011, an international consensus has been reached in Bologna on how to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. This article provides an objective assessment of the different treatment options currently available.A search of the database PUBMED was carried out for studies published in English between October 2000 and April 2016.There is no ideal protocol to manage poor responders even though the antagonist protocol seems to have an advantage of clinicians. This is thanks to better patient tolerance and reduced total dose of gonadotrophin as well as shorter time of stimulation. It seems that there is no benefit in increasing the gonadotrophin daily doses over 300IU nor using any specific type of gonadotrophin. Today, there is insufficient evidence to recommend any additional treatment for poor responders. Only dehydroepiandrosterone (DHEA) seems to increase embryonic quality and pregnancy rate, however further exploration and complementary prospective studies are necessary.New treatment strategies such as "oocyte banking" or double stimulation during the same cycle, could provide new prospects in poor responders management.

Objectifs L’infection par l’hpv a fait l’objet d’etudes aux resultats contradictoires concernant la survenue d’alteration du spermogramme, de fausses couches spontanees, de naissances avant terme et de diminution des taux de reussite en amp. La nature des genotypes d’hpv qui pourraient etre impliques dans des alterations du conceptus est encore debattue. Methodes Etude de cohorte, prospective, multicentrique, incluant 350 couples. Objectif principal Etudier l’association entre la presence d’une infection a hpv chez l’un des membres du couple (col uterin/sperme) et l’issue des grossesses obtenues en procreation medicalement assistee. La reussite de l’amp etait definie par l’obtention d’une grossesse aboutissant a la naissance d’un enfant viable et vivant. Objectifs secondaires Etudier les alterations du spermogramme, les genotypes specifiques d’hpv impliques, un lien potentiel entre hpv et les caracteristiques embryonnaires ainsi que la morbidite fœtale. L’analyse a ete realisee grâce a une modelisation avec ajustement sur un score de propension. Resultats Duree moyenne d’infertilite : 4,2 ± 2 ans. Moyenne d’âge des femmes 33 ± 4 ans, des hommes 36 ± 6 ans. Prise en charge : insemination intra-uterine dans 1,5 %, fiv dans 36,2 % et icsi dans 62,4 % des cas. Au moins un hpv etait present chez 26,9 % chez les femmes et 14,43 % chez les hommes. Un enfant vivant est ne dans 21,5 % des cas de meres hpv positives et dans 27,4 % de meres negatives (p = 0,3). Un enfant vivant est ne dans 36,6 % des cas de peres hpv positifs et dans 28,2 % de peres negatives (p = 0,2). Les couples exposes ont donne naissance dans 23,2 % a des enfants vivants et les couples non exposes dans 30,2 % des cas (p = 0,2). Vingt-cinq genotypes d’hpv ont ete trouves, les plus frequemment representes etaient a haut risque oncogene (16, 31, 51, 52, 53). Conclusion La presence d’hpv dans le sperme chez l’homme et/ou au niveau de l’endocol chez la femme ne constituait pas un facteur de risque d’echec en amp.

International audience; Circulating nucleic acids (cell-free DNA and microRNAs) have for particularity to be easily detectable in the biological fluids of the body. Therefore, they constitute biomarkers of interest in female and male infertility care. Indeed, in female, they can be used to detect ovarian reserve disorders (polycystic ovary syndrome and low functional ovarian reserve) as well as to assess follicular microenvironment quality. Moreover, in men, their expression levels can vary in case of spermatogenesis abnormalities. Finally, circulating nucleic acids have also the ability to predict successfully the quality of in vitro embryo development. Their multiple contributions during assisted reproductive technology (ART) make of them biomarkers of interest, for the development of new diagnostic and/or prognostic tests, applied to our specialty. Circulating nucleic acids would so offer the possibility of personalized medical care for infertile couples in ART.

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.

Cdc25C is a dual specificity phosphatase essential for dephosphorylation and activation of cyclin-dependent kinase 1 (cdk1), a prerequisite step for mitosis in all eucaryotes. Cdc25C activation requires phosphorylation on at least six sites including serine 214 (S214) which is essential for metaphase/anaphase transit. Here, we have investigated S214 phosphorylation during human meiosis with the objectives of determining if this mitotic phosphatase cdc25C participates in final meiotic divisions in human oocytes. One hundred forty-eight human oocytes from controlled ovarian stimulation protocols were stained for immunofluorescence: 33 germinal vesicle (GV), 37 metaphase stage I (MI), and 78 unfertilized metaphase stage II (MII). Results were stage dependent, identical, independent of infertility type, or stimulation protocol. During GV stages, phospho-cdc25C is localized at the oocyte periphery. During early meiosis I (MI), phosphorylated cdc25C is no longer detected until onset of meiosis I. Here, phospho-cdc25C localizes on interstitial microtubules and at the cell periphery corresponding to the point of polar body expulsion. As the first polar body reaches the periphery, phosphorylated cdc25C is localized at the junction corresponding to the mid body position. On polar body expulsion, the interior signal for phospho-cdc25C is lost, but remains clearly visible in the extruded polar body. In atresic or damaged oocytes, the polar body no longer stains for phospho-cdc25C. Human cdc25C is both present and phosphorylated during meiosis I and localizes in a fashion similar to that seen during human mitotic divisions implying that the involvement of cdc25C is conserved and functional in meiotic cells.

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.

Chromosomal abnormalities account for the majority of pre- and post- implantation embryo wastage in humans. Most of these abnormalities result from maternal meiotic errors, which preferentially occur during the first meiotic division. Consequently, the cytogenetic analysis of human oocytes has then been considered as a highly valuable source of data for the investigation of both the occurrence and the origin of chromosomal abnormalities in human. During the last 4 decades, the cytogenetic analysis of human oocytes has never stopped progressing, according to the advents of new technologies. Both karyotyping and molecular cytogenetic studies have been reported to date, providing a large body of data on the incidence and the distribution of chromosomal abnormalities in human female gametes. However, these studies display a great variability in results, which may be essentially attributable to the limitations of these techniques when applied to human oocytes. The most relevant analysis have led to the estimate that 15-20% of human oocytes present chromosome abnormalities, and they have emphasized the implication of both whole chromosome non-disjunction and chromatid separation in the occurrence of aneuploidy in human oocytes. The effect of advanced maternal age on the incidence of aneuploidy in human oocytes has also been clearly evidenced by recent reports based on large sample of oocytes or polar bodies.

BACKGROUND: The t(13;22) Robertsonian translocation constitutes a rare form of rearrangement between acrocentric human chromosomes. Most of the meiotic segregation studies of human Robertsonian translocations have been performed on common t(13;14) and t(14;21) translocations. Analysis of the chromosomal constitution in sperm of Robertsonian translocation carriers is of great interest for assessing the risk of unbalanced forms and adapting genetic counselling. In the present study, we present the first meiotic segregation study of a t(13;22) Robertsonian translocation in human sperm. METHODS: A total of 11 787 sperm nuclei were scored using two distinct FISH labelling techniques, i.e. the locus-specific probes (LSI) method and the whole chromosome painting (WCP) technique. RESULTS: The frequency of normal or balanced sperm resulting from alternate meiotic segregation was 86%. Incidences of unbalanced complements resulting from adjacent segregation modes were 12.79% and 14.36% in LSI and WCP assays, respectively. No significant excess of nullisomy or disomy for the affected chromosomes was observed. CONCLUSIONS: Similar results in segregation were obtained with the two techniques, demonstrating the efficiency of the two strategies for the direct segregation analysis of Roberstsonian translocations. The results obtained indicated a moderate meiotic production of imbalance. This study shows that the rare Robertsonian translocation (13;22) displays a similar distribution of balanced and unbalanced sperm patterns as the common Robertsonian translocations previously studied. This suggests that the behaviour of acrocentric chromosomes was similar in all cases of centric fusion.

The ovarian hyperstimulation treatment increases results of in vitro fertilization. However, the risk of ovarian hyperstimulation syndrome must be carefully evaluated for each patient. An excessive response increases complication and cancellation rates. Coasting could be applied when an excessive response occurred. This method requires stopping gonadotropin administration while GnRH agonist is continued. When the estradiol rate decreases, the hCG administration is allowed. In the literature, results shows adequate pregnancy rates, between 26 and 64%. It seems oocyte quality was not spoiled. However, coasting does not eliminate definitively the risk of ovarian hyperstimulation syndrome. Coasting method could be a safe and efficient method to treat an excessive ovarian response during in vitro fertilization protocol. Pregnancy rates seem to be preserved.

Obesity was defined by a body mass index more than 30 kg/m2. Many risks were related to this pathology, and sometimes, menstrual disorders or infertility. In order to obtain an adequate response to ovarian stimulation during IVF cycles, higher doses of menotropins are necessary in the group of obese patients. The mechanism of this phenomenon is still unclear. Leptin is one of the main hypothesis, and could act on obesity and reproductive system simultaneously. The likelihood to have an ongoing pregnancy after IVF treatment is less in the group of obese patients because of the increased risk of miscarriage and obstetrical complications. Weight loss prior IVF remains the main advice in order to decrease the risks of the procedure and to treat successfully these patients.

Serratia ficaria , an enterobacterium involved in the fig tree ecosystem, has been isolated from human clinical samples in rare instances, and its role as a pathogen is unclear. In 7 years, we have isolated S. ficaria from seven patients; it was the only pathogen in 4 patients, including a patient with septicemia described previously and three patients with gallbladder empyemas described in the present report. From March 1995 to July 1997, the incidence of biliary infections due to S. ficaria was 0.7%. We discuss the digestive carriage of this bacterium and its epidemiology with respect to the fig tree life cycle. Since fig trees grow around the Mediterranean as well as in the United States (California, Louisiana, Hawaii), S. ficaria should be more frequently isolated. In our experience, various strains have been misidentified or unidentified by commercial systems. Incorrect identification could be an additional explanation for the paucity of reported cases. S. ficaria produces nonpigmented, lactose-negative colonies which give off a potatolike odor. This odor is the primary feature of S. ficaria and must prompt reexamination of the identifications proposed by commercial systems. We tested 42 novel strains using three commercial systems: Vitek gram-negative identification (GNI) cards and API 20E and ID 32E strips (bioMérieux, Marcy-l’Etoile, France). The percentages of positivity that we have obtained were lower than those published previously for the following characteristics: lipase, gelatinase, DNase, and rhamnose. The best system for the recognition of S. ficaria is ID 32E, which correctly identified 27 of 42 strains. The API 20E system gave correct identifications for only two strains. S. ficaria was not present in the Vitek GNI card system database.