[What issues, changes and adaptations for French ART centers in the context of the new bioethics law?] / Quels enjeux et adaptations pour les centres d'AMP dans le cadre de la mise en place de la nouvelle loi de bioéthique ?

OBJECTIVE: This review intends to introduce the changes of the new Bioethics law in the reproductive field and its application in French ART centers. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[HLA-C KIR interactions and placental defects: Implications in ART pregnancy issues]. / Interactions HLA-C KIR et anomalies de la placentation : implications dans les issues de grossesses obtenues en AMP.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

[Assessment of genital microbiota: An emerging approach in assisted reproductive techniques]. / Évaluation du microbiote génital : une approche émergente en assistance médicale à la procréation.

The genital microbiota actively participates in women's reproductive health. Indeed, a genital dysbiosis (microbial imbalance associated with adverse effects on host health) can lead to vaginal infections (such as mycoses or bacterial vaginosis). Recent data reported that genital dysbiosis (e.g. vaginal or endometrial) was associated with fewer chances of live births in assisted reproductive technologies (ART), via decreased pregnancy rates and an increased risk of miscarriages. The presence or diversity of certain bacterial strains (in particular Gardenellavaginalis, Proteobacteria, Lactobacillusjensenii, Lactobacilluscrispatus or Atopobiumvaginae) within the genital microbiota seem to be associated with the outcomes of ART cycles, suggesting new approaches to improve ART results. In this review, we aim at presenting the state of art on the association between the female genital microbiota and ART success. The diagnostic and therapeutic approaches (i.e. probiotics, antibiotic therapy and transplantation of vaginal microbiota) in the management of patients with altered microbiota will also be discussed. The confirmation of these data in the coming years could significantly improve the management of infertile patients in ART with a more personalized approach partially based on the female genital microbiotic profile.

[Endometrial receptivity in assisted reproductive techniques: An aspect to investigate in embryo implantation failure]. / La réceptivité endométriale en aide médicale à la procréation : Une piste à ne pas oublier devant un échec d'implantation.

Infertility affects between 8 and 12% of reproductive-age couples worldwide. Despite improvements in assisted reproductive techniques (ART), live birth rates are still limited. In clinical practice, imaging and microscopy are currently widely used, but their diagnostic effectiveness remains limited. In research, the emergence of innovative techniques named OMICS would improve the identification of the implantation window, while progressing in the understanding of the pathophysiological mechanisms involved in embryo implantation failures. To date, transcriptomic analysis seems to be the most promising approach in clinical research. The objective of this review is to present the results obtained with the different approaches available in clinical practice and in research to assess endometrial receptivity in patients undergoing ART.

[Comparison of birth weights of children born after slow frozen embryo replacement versus fresh embryo transfer]. / Embryons vitrifiés, embryons frais : comparaison des poids de naissance.

OBJECTIVE: It is already known that children born after slow frozen embryo replacement have a significantly higher birth weight compared to children born after fresh embryo transfer. Similar data have been reported related to frozen embryo transfer using an open vitrification system. However, few data relative to birth weight using a complete embryo closed vitrification system has been reported. The purpose of this study was to know if frozen embryo in closed vitrification system is associated with a higher birth weight compared to fresh embryo replacement. DESIGN: This was a monocentric retrospective cohort study, 371 children were issued from fresh embryo replacement and 127 from vitrified embryo transfer. MATERIALS AND METHODS: All singletons born after fresh or vitrified embryo transfer between January 2011 and April 2015 were included. Births from the vitrified or fresh transfers of egg or sperm donation, and preimplantation genetic diagnosis were excluded. In addition, pregnancies with more than one gestational sac at the first ultrasound were excluded. An analysis of covariance (ANCOVA) was used for multivariate analysis. RESULTS: Mean birth weight was 205g higher in the frozen embryo compared with fresh embryos transfer groups (3368g vs. 3163g respectively, P<0.001). This difference remained after multivariate analysis adjusted on confounding factors such as gestational age, maternal age, maternal body mass index (BMI), tobacco exposure, number of embryo transferred and birth order (P<0.001).. CONCLUSIONS: Embryo frozen in closed vitrification system is associated with a higher birth weight compared to fresh embryo replacement. Our findings are consistent with the previous studies related to slow freezing and open vitrification systems data. The effects of controlled ovarian stimulation (COS), ex vivo culture conditions and cryopreservation systems on birth weight of children born should be further explored.

[Birth weight and frozen embryo transfer: State of the art]. / Poids de naissance et transfert d'embryon congelé : état de l'art.

The aim of this study was to update our acknowledgment if there is a link between assisted embryo cryopreservation and epigenetics in human? Animal studies have demonstrated epigenetics consequence and especially imprinting disorders due to in vitro culture. In human, it is important to note that after frozen embryo transfer birth weight is significantly increased by 81 to 250g. But these studies cannot identify the reasons of such difference. This review strongly suggests that embryo cryopreservation is responsible for birth weight variations but mechanisms not yet elucidated. Epigenetics is probably one of these but to date, none study is able to prove it. We have to be attentive on a possible link between assisted reproductive technology (ART) and epigenetics reprogrammation.

[Circulating nucleic acids and infertility]. / Les acides nucléiques circulants et infertilité.

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.