[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.

Combined FISH and PRINS sperm analysis of complex chromosome rearrangement t(1;19;13): an approach facilitating PGD.

Complex chromosome rearrangements (CCRs) are structural aberrations involving three or more breakpoints on two or more chromosomes. These CCRs result in a high rate of chromosome imbalances potentially leading to subfertility and congenital abnormality. In this study, we analysed meiotic segregation in the sperm of a patient with a familial CCR 46, XY,t(1;19;13)(p31;q13.2;q31)mat included in an intracytoplasmic sperm injection program because of oligoasthenozoospermia. The rearrangement was first identified using conventional and molecular cytogenetic methods. Primed in situ labelling (PRINS) and fluorescence in situ hybridization (FISH) techniques were then combined allowing the simultaneous use of five fluorochromes on the same sperm preparation, for the segregation analysis and the evaluation of the reproductive options for this patient. Segregation analysis was performed in a total of 1822 sperm nuclei from the translocation carrier. The percentage of unbalanced sperm was 75.9%, including 34.1% from 3:3 segregation, 38.2% from 4:2 segregation, 3.5% from 5:1 segregation and 0.05% from 6:0 segregation. Only 14.8% of sperm nuclei were consistent with a normal or balanced chromosome complement. In conclusion, chromosome segregation analysis combining FISH and PRINS was performed in sperm from a CCR carrier using five fluorochromes. These results advance our understanding of the mechanisms of meiotic segregation, and facilitate the assessment of the usefulness of preimplantation genetic diagnosis procedures in CCR couples.

Difficulties in providing palliative care in identified palliative care beds: An exploratory survey.

AIM: Identified Palliative Care Beds (Lits Identifiés Soins Palliatifs - LISPs) is a French specificity. Primarily created to integrate palliative care culture into conventional hospital units, the relevance of this measure became a controversial issue. Nowadays, hospital teams continue to frequently encounter complex situations regarding medical care for palliative patients. To the best of our knowledge, there is only one study, a quantitative one, bridging the gap about that subject. It showed failure in practicing palliative care work around LISP. Our study is based on a qualitative method that complements the quantitative study. It aimed to describe difficulties that limit palliative care practices in managing adult patients in LISP. METHOD: This qualitative exploratory survey was conducted with a sample of health service professionals (n=20), from senior physicians to caregivers. Each semi-structured interview included open questions regarding their experiences, feelings and difficulties with palliative care practices on LISP. It also included closed questions concerning interviewee's demographics and career course. The data for this research were submitted to a two-stage analysis: first, a global review of each interview was performed to identify trends. Then, a detailed breakdown, question by question, was implemented. RESULTS: From a quantitative perspective, the interviews revealed 305 difficulties, indicating the gaps and barriers limiting the implementation of a palliative approach in these services. From a qualitative perspective, five topics raised our attention by their recurrence in discourses: (1) partial knowledge about palliative care definition and legislation mostly due to a lack of training; (2) need for time; (3) need for human resources; (4) need for communication; (5) hard time in transitioning from curative to palliative care. PERSPECTIVE: This survey gives the opportunity to understand health service professionals' difficulties in practicing palliative care in conventional medical services. It raises the central issue of the pricing reform on the health institutes activity. It also provides angles of inquiry to improve LISP effectiveness. This qualitative and descriptive study was designed to explore difficulties in practicing palliative care around LISP. Nevertheless, according to the size of the sample, results will need to be confirmed by a more extensive qualitative survey.

[Oocyte and embryo quality: do the apoptotic markers have a place in the preimplantation genetic diagnostic?]. / Qualité ovocytaire et embryonnaire : les marqueurs apoptotiques ont-ils leur place dans le potentiel préimplantatoire ?

In Assisted Reproductive Technology (ART), the pregnancy and birth rates following in vitro fertilization (IVF) attempts are still low. Recently, research in the field of ART has explored new oocyte and embryo quality selection criteria such as apoptotic markers. Many studies provided evidence that bad oocyte and embryo quality can be associated with apoptosis. The aim of this review is to summarize our current knowledge on the apoptosis process in oocytes and embryos, and focus on the possibility of using apoptotic markers as a reliable and predictive marker to select competent oocytes and embryos during IFV.

[Natural cycle in vitro fertilization cycle in poor responders]. / Le cycle naturel en fécondation in vitro chez les mauvaises répondeuses.

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.

[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.

[Oncofertility program at the Montpellier university hospital 2 years after]. / Programme de préservation de la fertilité féminine au CHRU de Montpellier 2ans après.

OBJECTIVE: Female fertility preservation in the context of cancer management is crucial for patient's health care. The aim of this study was to evaluate the oncofertility practice at our university hospital of Montpellier since 2011. PATIENTS AND METHODS: The evaluation of management of young patients referred to Montpellier University Hospital from September 2011 to September 2013 for oncofertility counselling before cancer treatment. RESULTS: Seventy-one patients were referred to a specialized oncofertility center. Forty-two patients (59.1%) were included in the oncofertility program. Twenty-two patients (31%) were proposed for oocyte vitrification after COS protocol, eight patients (11.3%) for ovarian tissue cryoconservation, seven patients (9.9%) for GnRH injections, three patients (4.2%) ovarian transposition and two patients (2.8%) for embryo cryopreservation. Among the 42 indications of fertility preservation, only 18 will have finally taken place. CONCLUSION: Oncofertility counselling for young patients should now be part of the cancer management. It involves multidisciplinary teams. Further information of both oncologists and patients is needed to improve this new approach in the field of cancer treatments.