Increased pregnancy rate using standardized coculture on autologous endometrial cells and single blastocyst transfer : a multicentre randomized controlled trial.

Despite excellent published results, the lack of well-designed, multicentre, randomized clinical trials results in an absence of general consensus on the efficacy of autologous endometrial cells coculture (AECC) in Assisted Reproductive Technology (ART). An open, multicentre, prospective, randomized controlled trial was designed to compare the pregnancy rate (PR) after the transfer of one blastocyst on day 5 after AECC to the transfer of one embryo on day 3 (control group). Patients were women aged 18 to 36, undergoing an ART cycle with no more than 1 embryo transfer failure. Sample size was calculated at 720 for a superiority trial involving an intermediate analysis at 300 patients. We present the results of the intermediate analysis that resulted in the study ending considering the observed difference. Three hundred thirty nine patients were randomized: 170 in the AECC group and 169 in the control group. The clinical PR per transfer was 53.4% with AECC and 37.3% in the control group (p=0.025). The quality of embryos was improved with AECC. These results suggest that implementation of the AECC technique to a large number of In-Vitro Fertilization (IVF) centres could lead to a substantial improvement in the proportion of successful assisted reproduction. The study was supported by the Laboratoires Genévrier, France.

[EUGIC (Extension of the Use of Gametes in Intra-Conjugal): New uses of gametes within the couple]. / EUGIC (Extension de l'Utilisation de Gamètes en IntraConjugal) : les nouveaux usages des gamètes au sein du couple.

OBJECTIVE: New possibilities for using gametes within a couple were created by the French law of August 2, 2021 related to bioethics by opening Assisted Reproductive Technics (ART) to all women. It concerns previously self-preserved gametes, thus avoiding the need for gamete donation. The objective of our study is to evaluate the perception of these new uses by ART practitioners. METHOD: A questionnaire of twelve short questions was sent to professionals concerned with gamete donation. RESULTS: One hundred and ten professionals answered the questionnaire. The majority of them approve of the Reception of Oocytes from the Partner (ROPA), notably if there is a medical indication. Requests are rarer for the care of trans* people, and raise more questions. Although less favorable to the use of eggs from trans* men, more of them support the practice when it is an alternative to oocyte donation. CONCLUSION: The acronym EUGIC (Extension of the Use of Gametes in Intra-Conjugal) makes it possible to group together these new situations generated by the change in the French law.

Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance.

Myeloid antigen-presenting cells (APC) are known to cross-present exogenous antigen on major histocompatibility class I molecules to CD8+ T cells and thereby induce protective immunity against infecting microorganisms. Here we report that liver sinusoidal endothelial cells (LSEC) are organ-resident, non-myeloid APC capable of cross-presenting soluble exogenous antigen to CD8+ T cells. Though LSEC employ similar molecular mechanisms for cross-presentation as dendritic cells, the outcome of cross-presentation by LSEC is CD8+ T cell tolerance rather than immunity. As uptake of circulating antigens into LSEC occurs efficiently in vivo, it is likely that cross-presentation by LSEC contributes to CD8+ T cell tolerance observed in situations where soluble antigen is present in the circulation.

[Comparative survey of French oocyte donor's profile and motivations between nulliparous and multiparous donors, 2017-2018]. / Profils et motivations des donneuses d'ovocytes en France en 2017­2018 : comparaison entre les nullipares et celles qui ont déjà procréé.

OBJECTIVES: Since the authorization of French nulliparous women to donate oocytes, who are the new donors? What are the similar and differential points with the initial donors who have already procreated? METHODS: Retrospective multicenter cohort study using a questionnaire. RESULTS: The return rate is 90.7% with 248 donor files from 5 French assisted reproductive technology (ART) centers, included between 1 January 2017 and 31 December 2018. The average age is 31,0 years. More than two thirds of women have a higher educational level than the license. Donation is spontaneous or relational in 69% and 25% of cases, respectively. Among nulliparous donors, 37% don't know the possibility of self-preservation but after information, 80% wish to benefit from it versus 32% of multiparous women if they were given the opportunity. CONCLUSIONS: This study by the Study Group for Egg Donation (GEDO) highlights the particularities of French oocytes donors. The 2015 decree allowed to diversify the origin of the donation, which remains mainly altruistic but the possibility of self-preservation for nulliparous donors also seems to motivate women. This link between donation and self-preservation poses an ethical problem that needs to be approached and resolved in the next Bioethics Law framing Assisted Reproductive Technologies (ART).

[Embryo transfer in case of stenosed and/or forbidding cervix]. / Transfert embryonnaire en cas de col sténosé et/ou infranchissable.

A cervical stenosis can follow an infection, a conisation or a trachelectomy and lead to a cervical infertility. In in vitro fertilization (IVF), embryo transfers are difficult in case of a cervical stenosis and specific care is required. Treatments try to restore an adequate cervical patency. Repeated cervical dilatations can represent a solution. In case of inefficiency, a new cervicoisthmic opening has to be created with surgery. Perpetuity of the result is obtained thanks to post surgical dilatations or thanks to implementation of an intracervical catheter till complete cicatrization. In case of failure of canalization of the stenosed isthmic os, alternative treatments can be proposed. Intraperitoneal insemination in the poutch of Douglas is interesting when tubes are patent and when semen quality is sufficient. On the contrary, transmyometrial embryo transfer and gametes or zygotes intrafallopian transfer represent an ultimate therapeutic option.

[Impact of infertility and assisted reproductive techniques on sexuality]. / Impact de l'infertilité et de l'Assistance médicale à la procréation sur la sexualité.

OBJECTIVE: We studied the impact of infertility and all the more Assisted Reproductive Techniques on marital relations and sexuality. MATERIAL AND METHOD: Our study is based on a questionnaire distributed in our centre and on a review of literature. RESULTS: Our inquest shows that both partners keep a good relationship in their couple and support each other. But, whereas pleasure during intercourse is little affected, many couples feel a reduction of their desires. DISCUSSION AND CONCLUSION: This diminution of sexual desires, also noted in literature, can be explained by medical requirements intrusive for intimacy and also by strategies settled by the couples themselves during intercourse in order to optimise the chance of pregnancy. Medical staffs should take into consideration eventual sexual difficulties of the couples. Making them aware that their intimate life must remain or become again an end in itself, and not only a way of procreation, often permits a beneficial change of behaviour.

[Does sexuality still have a place for couples treated with assisted reproductive techniques?]. / Reste-t-il de la place pour la sexualité lors de la prise en charge en assistance médicale à la procréation ?

METHOD: This research enabled us to study the links between the diagnosis of infertility, medical care and the sexuality of the couples treated with Assisted Reproductive Techniques (ART). QUESTIONNAIRE/PATIENTS: The impact of infertility has been observed in various fields related to sexual intercourse: sexual desire and satisfaction, frequency of intercourse, sexual disorders as well as marital relationship and more generally the patient's experience of this medical follow-up. These effects were studied in the light of various factors, such as sex and age, number of children and years of ART as well as the type of protocol and the origin of infertility. RESULTS: Our study reveals that the marital relationship is preserved as well as the pleasure felt during intercourse. However, the couples express a reduction of their sexual desire, linked to a loss of spontaneity that can be related to the strategies they set up to maximize their chances of pregnancy and to medical care.

[Oocyte donation in Turner syndrome]. / Don d'ovocytes et syndrome de Turner.

Turner syndrome represents about 10% of the indications of oocyte donation. Pregnancy rates are as satisfactory as for other indications when endometrial preparation is sufficient. Unfortunately patients with Turner syndrome present somatic abnormalities inducing obstetrical complications and even an elevated mortality rate, in particular by aortic dissection. So, it is absolutely necessary to define with extreme precision the elements of medical check up previous to oocyte donation as well as the forms of medical care during pregnancy which would protect the patients from severe complications.

[The desire to become a parent when infected with human immunodeficiency virus, hepatitis C virus or hepatitis B virus]. / Désir d'enfant et infections virales: hépatites C et B et virus de l'immunodéficience humaine.

The French law (arrêté du 10 mai 2001) allows Assisted Reproductive Techniques (ART) in case of infection with human immunodeficiency virus, hepatitis C virus or hepatitis B virus. Our six years' experience is positive even if pluridisciplinary care needs specific equipment and human forces. Couples express high motivation. The wish to become a parent leads to a better care of the infection. ART results are excellent in case of male contamination, not as good when the female partner is infected but still encouraging. No contamination of the partner or the offspring occurred after ART. Data are already collected in France in this context. A European register should be constituted in an early future.

[Embryo donation in France: practice and difficulties. Strasbourg's experience]. / L'accueil d'embryon en France: pratiques et difficultés. L'expérience de Strasbourg.

OBJECTIVE: The aim of this study was to present the situation of embryo donation in France and around the world, to expound the difficulties of its practice and the results obtained in our centre 3 years after the introduction of this procedure. PATIENTS AND METHODS: Embryo donation in France is controlled by implemented decrees published between 1999 and 2004. The couples, who have stored frozen embryos since at least two years, were contacted for a pluridisciplinary medical consultation. The indication of embryo donation was evaluated for the recipients through a pluridisciplinary approach. RESULTS: Among the interviewed couples, 16.7% have chosen embryo donation but only half of them have completed the procedure (6% of the couples with frozen embryos). The main indications for embryo donation were a double sterility, unexplained genetic disease, ART failures (poor fertilization or bad embryo quality) and oocyte donation when the delay was too long for the couples. The pregnancy rate was 28.6% after the 21 first embryo transfers. DISCUSSION AND CONCLUSION: The results of embryo donation confirm the international experience both considering the poor number of donated embryos, medical indications and results. Embryo donation has its place among ART techniques, but one should not ignore the general debate on ethical questions raised by this procedure.

[Does fertility treatment increase the risk of breast cancer? Current knowledge and meta-analysis]. / Les traitements inducteurs de l'ovulation augmentent-t-ils le risque de cancer du sein ? Mise au point et méta-analyse.

OBJECTIVE: The objective of this review was to assess the level of risk of breast cancer for women exposed to ovulation-inducing therapy (OIT). METHODS: The 25 selected studies were extracted from the PUBMED database from January 2000 until March 2016 with the following key-words: "fertility agents", "infertility treatments", "clomiphene citrate", "buserelin", "ovarian stimulation", "assisted reproductive technology" and "breast cancer". Our meta-analysis was performed using Review Manager software, Cochrane Collaboration, 2014. The results were calculated by type of OIT, as well as globally. RESULTS: The analysis of these published epidemiological studies confirms that exposition to OIT is not a breast cancer risk factor, but the results are contradictory. Two studies have shown a significantly increased risk of breast cancer in a population of infertile women, while two others have found a significant decrease of this risk. The twenty others did not show any impact of IOT over this risk. Our meta-analysis of 20 selected studies has not identified a significant association between exposition to OIT and breast cancer risk (relative risk=0,96; IC 95: (0,81-1,14) for cohort studies and odds ratio=0,94; IC 95% (0,81-1,10) for case-control studies). CONCLUSION: Exposition to OIT is not an identified risk factor for breast cancer. A message reassuring about a possible risk of OIT-related breast cancer should be given to these women. Exposition to OIT is therefore not an indication of increased breast surveillance.

[Intra-uterine insemination at either 24 or 48hours after ovulation induction: Pregnancy and birth rates]. / Insémination intra-utérine à 24 ou 48heures du déclenchement de l'ovulation : taux de grossesse et d'accouchement.

OBJECTIVE: Comparing rates of pregnancy and childbirth between IUI at either 24 or 48hours after injection of HCG. METHODS: This is a single-center retrospective study of couples who underwent intrauterine insemination between January 2013 and December 2014 at Medical-Surgical Obstetrical Centre of Schiltigheim. Stimulation of ovulation was done by FSH or HMG, and ovulation induction by 250µg of recombinant HCG. The insemination was performed after 2 days (group D2) or the day after (group D1). RESULTS: Among the 1092 intrauterine insemination cycles included in our study, 62 were done the day after ovulation induction by HCG (D1), and 1030 the day after (D2). Our study showed no significant difference in the rate of biological pregnancy, defined by a rate of BHCG>15IU/L, between the group D1 (19.35%) and the group D2 (18.12%), P=0.94, and no difference in live birth rate: respectively 14,50% and 11.75%, P=0.18. CONCLUSION: Our study reported similar rates of pregnancy and childbirth in the group who underwent IUI at D1 and D2 of ovulation induction, suggesting the possibility of IUI on day 1 when the organization of the service needs it, without loss of opportunity for pregnancy.

[Infertility and breast cancer: Is there a link? Updated review of the literature and meta-analysis]. / L'infertilité est-elle un facteur de risque de cancer du sein ? Revue actualisée de la littérature et méta-analyse.

UNLABELLED: The objective of this review was to assess the level of risk of breast cancer of patients consulting for infertility. METHODS: Studies of cohorts and case-control were extracted from the Pubmed database from January 2000 until May 2015 through the following keywords: "infertility"; "endometriosis"; "polycystic ovary syndrome"; "breast cancer", "cancer risk". Eleven publications were finally selected after exclusion of publications dealing with infertility after breast cancer. Our meta-analysis, involving 10 of these publications, was performed using Review Manager software, Cochrane Collaboration, 2014. The results were calculated by etiology of infertility, polycystic ovary syndrome (PCOS) and endometriosis, as well as globally. RESULTS: The analysis of these published epidemiological studies confirms that infertility is not a breast cancer risk factor, but the results are contradictory. Three studies have shown a significantly increased risk of breast cancer in a population of infertile women, while 7 others have not found this risk. These contradictions are due to the heterogeneity of the studies, the included populations, the follow-up periods and confounding factors. Our meta-analysis of the selected studies has not identified a significant association between infertility and breast cancer risk (1.05; 95% CI [0.96-1.16]). A subgroup analysis on endometriosis and PCOS showed no significant association either, with an OR of 1.02 (95% CI [0.87-1.19]) and 1.19 (95% CI [0.93-1.51]), respectively. CONCLUSION: Infertility is not an identified risk factor for breast cancer. A message reassuring about a possible risk of infertility-related breast cancer should be given to these patients. Infertility is therefore not an indication of increased breast surveillance.

[Patient's experience of topical anesthesia by lidocaine vaginal gel for oocyte retrieval]. / Anesthésie topique par gel de lidocaïne intravaginal pour ponction ovocytaire : retour d'expérience.

A recent adverse effect of a paracervical block (cardiac arrest) occurred during an oocyte retrieval (OR), forcing us to reconsider our pain management during OR. Since then, we decided to use intravaginal lidocaine gel as analgesia during OR. OBJECTIVES: To evaluate the pain during OR after intravaginal lidocaine gel analgesia and to evaluate the motivations of women choosing this technique. METHODS: A monocentric observational study was performed on 200 patients. Pain was measured using a numeric pain scale during and after oocyte retrieval. The tolerance of the procedure was evaluated through a patient questionnaire. RESULTS: Median maximal pain was 5±2.3 (0-10) per-retrieval and 3±2.2 (0-10) post-retrieval. The procedure was considered bearable by 85.5% of the patients and 81.5% of them would choose this method in case of new oocyte retrieval. No adverse effect occurred during the study. CONCLUSION: The use of intravaginal lidocaine gel seems an acceptable analgesia alternative during oocyte retrieval.

[Age of puberty and western young women sexuality]. / Âge de la puberté et sexualité des jeunes femmes occidentales.

The onset of menarche and age of first sexual experience have both lowered over the past century. Does the age of puberty influence the sexuality of the girl/young occidental woman? If so, to what degree? Besides, is the acquisition of reproductive function, regardless of age, a sign of sufficient maturity to engage in sexual activity? Studies show that early puberty, early sex, unprotected sexual intercourse in adolescence and number of sexual partners in early adulthood are closely related. These early sexual experiences could be stimulated by early drug use as well as by depressive disorders. The age of puberty has a real influence on sexuality but this link will be modulated by a number of social behavioral factors and it is not sustainable. The age of puberty is not a good indicator of maturity for teenage sexuality; early maturation and early sexual activity are usually associated with risky behaviors. However, other studies on the subject are required, including a consideration of the issues associated with delayed puberty, a subject virtually absent from the literature.

[Future perspectives: oocyte cryopreservation and in vitro maturation]. / Perspectives d'avenir: la congélation et la maturation in vitro des ovocytes.

After treatment for neoplasia, a young patient can nowadays hope to be pregnant. The aim of this paper is to establish a review of the literature about cryopreservation of oocytes and ovarian tissue, and in vitro maturation of oocytes. These studies also concern patients for which ovarian stimulation is difficult, such as PCOS. These techniques could also facilitate the creation of an oocyte bank as the one already existing for sperm. So far the main studies published, in spite of very timid first results, allow us to look to a great future for cryopreservation and in vitro maturation of oocytes.

[Towards a single embryo transfer: predictive value of uterine and embryological parameters in assisted reproduction outcome]. / Vers un transfert mono-embryonnaire : prise en compte conjointe des paramètres embryonnaires et utérins en assistance médicale à la procréation.

OBJECTIVE: The transfer of a single embryo would avoid obstetrical and neonatal complications due to multiple pregnancies. We studied the clinical value of both uterine and embryological parameters to define precise conditions allowing a single embryo transfer without decreasing pregnancy rates. PATIENTS AND METHODS: Endometrial parameters expressed by a uterine score together with biological criteria of 131 in vitro fertilization or intracytoplasmic sperm injection attempts were retrospectively analysed. RESULTS: Two hundred and sixty-two day-3 embryos were replaced through 131 transfers. Fifty-seven pregnancies were induced and 16 twins were obtained. The clinical pregnancy rate was 35.9% and the embryonic implantation rate 24.0%. After the transfer of two embryos, successful implantation was determined by the occurrence of top-quality embryos and simultaneously by a receptive endometrium. The uterine pulsatility index was significantly decreased for twin compared to singleton pregnancies. DISCUSSION AND CONCLUSION: This study confirms that a uterine score constitutes a powerful tool for evaluating the uterine receptivity. This parameter has to be taken into account as well as the embryonic quality, in order to optimise the success rate. Young patients with at least two top-quality embryos available, a high uterine score and a low pulsatility index, have a high risk of multiple births and are suitable for a single-embryo transfer.

[Abnormal bacterial colonisation of the vagina and implantation during assisted reproduction]. / Colonisation bactérienne vaginale anormale et implantation en assistance médicale à la procréation.

OBJECTIVE: To evaluate the efficiency of our treatment of vaginal infection for couples included in an IVF program. PATIENTS AND METHODS: Microbiologic screening of vaginal flora and semen has been performed one month prior to in vitro fertilization for 951 couples in 2000. Antibiotic treatment was prescribed in case of positive culture. RESULTS: Positive microbial growths were observed from endocervical and vaginal cultures in 218 women (22.9%). The clinical pregnancy rate was 30.29% in the group of patients without growth and 30.27% in the group with positive microbial growth. The implantation rate was significantly diminished in case of bacterial growth: 14.6 compared to 19.3% (P <0.02) for sterile endocervical culture. Five main bacterial species were found at the cervical level: Candida albicans (69 cases), Ureaplasma urealyticum (49 cases), Gardnerella vaginalis (43 cases), Streptococcus B or D (24 cases) and Escherichia coli (22 cases). Positive cultures from both vagina and semen were observed for 77 couples whose clinical pregnancy rate was 19.5 vs 36.2% in case of vaginal infection alone (P <0.01) with a spontaneous miscarriage rate of 46.7 compared to 17.6% (P <0.01). DISCUSSION AND CONCLUSION: Endocervical microorganisms, even treated with adapted antibiotics, may affect embryonic implantation. Positive culture from both female and male partner may enhance this negative effect. In this case, the best strategy would be to cancel the IVF treatment.

[Twin birth after preimplantation diagnosis for cystic fibrosis]. / Naissance gémellaire après diagnostic préimplantatoire pour mucoviscidose.

OBJECTIVE: Cystic fibrosis is a common autosomal recessive disease most often caused by a deletion (delta F508) in the CFTR gene. It is the most common indication for preimplantaion genetic diagnosis which allows genetic analysis of embryos obtained after in vitro fertilization and transfer of unaffected embryos into the patient's uterus. PATIENTS AND METHODS: We report the first preimplantation genetic diagnosis performed in Strasbourg for a couple at risk of having a child affected by severe cystic fibrosis due to a homozygous delta F508 mutation. Three days after fertilisation, embryos obtained after intra-cytoplasmic testiculare sperm injection were biopsied and analysed. PCR amplification of the genomic fragment containing the delta F508 locus allowed detection of the delta F508 mutation and transfer only of the unaffected embryos. RESULTS: Three embryos were transferred after this preimplantation genetic diagnosis. A twin pregnancy was obtained and the babies born from this cycle are both exempt from the mutation. CONCLUSIONS: Preimplantation genetic diagnosis for the cystic fibrosis delta F508 mutation is now available in our centre. In this report, we could resolve both the problem of infertility and the risk of transmission of a severe form of cystic fibrosis. Preimplantation genetic diagnosis is also available for other mutations involved in cystic fibrosis and also for other genetic diseases.

[Evolution of homocysteine during ovarian stimulation for IVF or ICSI]. / Evolution de l'homocystéine lors d'un cycle d'induction ovarienne pour FIV ou ICSI.

OBJECTIVE: To determine the homocysteine evolution during ovarian stimulation in IVF or ICSI protocols and in, a second time, to evaluate the role of hyperhomocysteine as thrombotic risk factor for the treated patients. MATERIAL AND METHODS: Plasma homocysteine was determined three times for each of 31 women included in an IVF/ICSI program. Dosages were realised before stimulation, after gonadotrophin-releasing hormone agonist treatment (GnRH) and on the day of hCG injection. Vitamin B12 and folates were determined before stimulation. In case of hyperhomocysteinemia, a research of APCR (Activated Protein C Resistance) was realised. RESULTS: Five hyperhomocysteinemia cases were discovered (16.12% of studied population). APCR was found in a patient with hyperhomocysteinemia (14 mumol/L, before stimulation). Molecular biology has confirmed an heterozygous mutation of factor V Leiden. During the ovarian stimulation the evolution of homocysteine was independent of the 17 beta oestradiol evolution. CONCLUSION: The prevalence of hyperhomocysteinemia was not significative according to the limited size of the studied population. The increase of oestradiol during induction protocols is unrelated to the homocysteine level. This work must be continued with largest population to have better knowledge of the prevalence of hyperhomocysteinemia among women included in ovarian stimulation protocols.