Serum androgen dynamics in young women aged 18-40 treated with chemotherapy for breast cancer: an observational, multicentric, prospective study in France.

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464.

[Pre-implantation genetic testing: Comparison between cleavage stage and blastocyst biopsy]. / Le diagnostic préimplantatoire : comparaison des stratégies de biopsie embryonnaire au stade clivé et au stade blastocyste.

OBJECTIVES: Preimplantation genetic testing (PGT) refers to the set of techniques for testing whether embryos obtained through in vitro fertilization have genetic defect. There is a lack of global standardization regarding practices between countries or even from one center to another. In ours, biopsies are preferably performed on day 3 embryos, but also at the blastocyst stage on day 5. The blastocyst biopsy often requires systematic freezing of the embryos before obtaining the genetic results, whereas day 3 biopsy allows fresh embryo transfer of the healthy or balanced embryo after getting the genetic results. We wanted to compare the chances of success for couples performing PGT in our center according to the day of the biopsy. METHODS: For this, we carried out a retrospective monocentric study including all PGT cycles performed between 2016 and 2019 divided into two groups: day 3 or day 5 biopsy. RESULTS: There was no significant difference in terms of live birth rate (P=0.7375) after fresh embryo transfers, as well for pregnancy rates, clinical pregnancy rates, implantation rates and miscarriage rates. On the other hand, we observed higher live birth rates after frozen-thawed embryo transfer when the biopsy was performed on day 5 rather on day 3 (P=0.0001). We also wanted to assess what was the most efficient biopsy strategy in our laboratory. Our rates of useful embryos were similar regardless of the day of the biopsy (34% in D3 and 37.7% in D5, P=0.244). No statistical difference was found in the number of unnecessarily biopsied embryos in the two groups. But still, the percentage of embryos biopsied on D5 and immediately frozen was 42.8% (118 blastocysts), while no embryo biopsied on D3 led to this case. CONCLUSION: Therefore, our results are in favor of generalization of the D5 biopsy as the international standard. However, the organizational, financial and logistical implications that this technic would impose make it unsystematic in our center.

Evolution of serum Anti-Müllerian Hormone (AMH) level in young women treated with chemotherapy for breast cancer according to basal AMH level.

OBJECTIVE: Serum AMH level has been shown to decrease in women treated for breast cancer in several studies. However, whether basal AMH status affects AMH dynamics during chemotherapy remains to be clarified. The objective of this study was to compare serum AMH dynamics in young women with either low, normal or high basal serum AMH level at diagnosis, during and after treatment with chemotherapy for breast cancer. STUDY DESIGN: In this secondary analysis of a prospective cohort study, serum AMH was measured during and after chemotherapy in 239 women of reproductive age diagnosed with breast cancer and treated with chemotherapy. The association between AMH dynamics throughout chemotherapy and during follow-up and basal AMH status, i.e. low AMH (<1 µg/l, <7 pmol/l), normal AMH (1-4.9 µg/l, 7-36 pmol/l) and high AMH (≥5 µg/l, >36 pmol/l), was evaluated. Menses occurrence was also recorded. RESULTS: A total of 21 women had low, 154 had normal and 64 had high basal AMH level. Serum AMH rapidly decreased during chemotherapy in all groups, and its variation during chemotherapy and follow-up was not significantly different between the 3 groups. CONCLUSION: No association was found between AMH variation during chemotherapy and follow-up, and basal AMH level at diagnosis. However, women with high basal AMH levels have significantly higher AMH levels throughout chemotherapy and follow-up than women with normal or low basal AMH levels at diagnosis.

Female obesity does not impact live birth rate after frozen-thawed blastocyst transfer.

STUDY QUESTION: Does female obesity affect live birth rate after frozen-thawed blastocyst transfer? SUMMARY ANSWER: Live birth rate was not statistically different between obese and normal weight patients after frozen-thawed blastocyst transfer (FBT). WHAT IS KNOWN ALREADY: Obesity is a major health problem across the world, especially in women of reproductive age. It impacts both spontaneous fertility and clinical outcomes after assisted reproductive technology. However, the respective impact of female obesity on oocyte quality and endometrial receptivity remains unclear. While several studies showed that live birth rate was decreased in obese women after fresh embryo transfer in IVF cycle, only two studies have evaluated the effects of female body mass index (BMI) on pregnancy outcomes after frozen-thawed blastocyst transfer (FBT), reporting conflicting data. STUDY DESIGN, SIZE, DURATION: This retrospective case control study was conducted in all consecutive frozen-thawed autologous blastocyst transfer (FBT) cycles conducted between 2012 and 2017 in a single university-based centre. A total of 1415 FBT cycles performed in normal weight women (BMI = 18.5-24.9 kg/m2) and 252 FBT cycles performed in obese women (BMI ≥ 30 kg/m2) were included in the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial preparation was standard and based on hormonal replacement therapy. One or two blastocysts were transferred according to couple's history and embryo quality. MAIN RESULTS AND THE ROLE OF CHANCE: Female and male age, smoking status, basal AMH level and type of infertility were comparable in obese and normal weight groups. Concerning FBT cycles, the duration of hormonal treatment, the stage and number of embryos (84% single blastocyst transfer and 16% double blastocysts transfer) used for transfer were comparable between both groups. Mean endometrium thickness was significantly higher in obese than in normal weight group (8.7 ± 1.8 vs 8.1 ± 1.6 mm, P < 0.0001). Concerning FBT cycle outcomes, implantation rate, clinical pregnancy rate and live birth rate were comparable in obese and in normal weight groups. Odds ratio (OR) demonstrated no association between live birth rate after FBT and female BMI (OR = 0.92, CI 0.61-1.38, P = 0.68). LIMITATIONS, REASONS FOR CAUTION: Anthropometric parameters such as hip to waist ratio were not used. Polycystic ovarian syndrome status was not included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: Our study showed that live birth rate after frozen-thawed blastocyst transfer was not statistically different in obese and in normal-weight women. Although this needs confirmation, this suggests that the impairment of uterine receptivity observed in obese women after fresh embryo transfer might be associated with ovarian stimulation and its hormonal perturbations rather than with oocyte/embryo quality. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Development of automated annotation software for human embryo morphokinetics.

STUDY QUESTION: Is it possible to develop an automated annotation tool for human embryo development in time-lapse devices based on image analysis? SUMMARY ANSWER: We developed and validated an automated software for the annotation of human embryo morphokinetic parameters, having a good concordance with expert manual annotation on 701 time-lapse videos. WHAT IS KNOWN ALREADY: Morphokinetic parameters obtained with time-lapse devices are increasingly used for the assessment of human embryo quality. However, their annotation is time-consuming and can be slightly operator-dependent, highlighting the need to develop fully automated approaches. STUDY DESIGN, SIZE, DURATION: This monocentric study was conducted on 701 videos originating from 584 couples undergoing IVF with embryo culture in a time-lapse device. The only selection criterion was that the duration of the video must be over 60 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: An automated morphokinetic annotation tool was developed based on gray level coefficient of variation and detection of the thickness of the zona pellucida. The detection of cellular events obtained with the automated tool was compared with those obtained manually by trained experts in clinical settings. MAIN RESULTS AND THE ROLE OF CHANCE: Although some differences were found when embryos were considered individually, we found an overall concordance between automated and manual annotation of human embryo morphokinetics from fertilization to expanded blastocyst stage (r2 = 0.92). LIMITATIONS, REASONS FOR CAUTION: These results should undergo multicentric external evaluation in order to test the overall performance of the annotation tool. Getting access to the export of 3D videos would enhance the quality of the correlation with the same algorithm and its extension to the 3D regions of interest. A technical limitation of our work lies within the duration of the video. The more embryo stages the video contains, the more information the script has to identify them correctly. WIDER IMPLICATIONS OF THE FINDINGS: Our system paves the way for high-throughput analysis of multicentric morphokinetic databases, providing new insights into the clinical value of morphokinetics as a predictor of embryo quality and implantation. STUDY FUNDING/COMPETING INTEREST(S): This study was partly funded by Finox-Gedeon Richter Forward Grant 2016 and NeXT (ANR-16-IDEX-0007). We have no conflict of interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Ultrasonographic measures of body fatness and their relationship with plasma levels and adipose tissue expression of four adipokines in Welsh pony mares.

Obesity is responsible for metabolic dysregulations that alter fertility and induce pathologies. The objectives of the present study were to validate a reliable method for the evaluation of body fatness in mares and to associate the body fat estimation data to metabolic changes, including adipokines at the plasma and adipose tissue levels. To reach this purpose, animals were subjected to two extreme breeding conditions to study the variation of morphological, ultrasound, and physiological parameters. Twenty Welsh mares were followed up monthly from April to October before and after animals were moved outdoors to grasslands. Body weight (BW), body length (BL), height at the withers (HW), thoracic perimeter (TP), 5-point body condition score (BCS), and subcutaneous fat thickness (SFT) at the level of the shoulder, the lumbar region, and the rump, measured by ultrasonography, and plasma and adipose tissue metabolic indicators were assessed in parallel. Statistical analysis was performed using a linear mixed-effects model, whereas Pearson tests were used for the analysis of the correlations between the different parameters. Although mean BW did not increase significantly (P = 0.0940), TP (P = 0.0002) and BCS (P < 0.0001) increased during the study period. Ultrasonographic examination of subcutaneous adipose tissue showed an increase in SFT at the level of the shoulder (P < 0.0001), lumbar region (P < 0.0001), and rump (P < 0.0001). Plasma concentrations of nonesterified fatty acids (P < 0.0001), phospholipids (P < 0.0001), and cholesterol (P < 0.0001) increased significantly, whereas triglycerides (P < 0.0001) decreased significantly during the study period. Although both plasma concentrations and adipose tissue expression of leptin (P < 0.0001) and resistin (P < 0.0001) increased significantly, adiponectin (P < 0.0001) significantly decreased and visfatin remained unchanged (P = 0.8401). Expression of adipokine receptors studied showed the opposite pattern compared with their ligand. Ultrasonographic measurements of subcutaneous adipose tissue thickness at the shoulder, lumbar region, and rump are relevant indicators of fatness related with adipokine plasma concentrations and expression of adipokine-related receptors in adipose tissue, and particularly highlight seasonal effects.

Sperm cryopreservation and assisted reproductive technology outcome in patients with spinal cord injury.

This study aimed to describe spinal cord injured patients' semen characteristics before and after cryopreservation, and assisted reproductive technology cycles outcome compared to the infertile population. Data about sperm analysis and assisted reproductive technology (ART) cycles outcomes for 78 men with spinal cord injury referred for sperm cryopreservation between 1998 and 2013 were retrospectively analysed and compared with a reference group consisting of every Intra Cytoplasmic Sperm Injection (ICSI) cycle performed in our in vitro fertilization unit over the 2009-2014 period. Semen was collected by penile vibratory stimulation (PVS), electroejaculation or via testis biopsies. Fresh and frozen semen parameters and ART outcomes with frozen-thawed sperm were measured. Patients were divided into three groups according to the sperm retrieval methods: 37 electroejaculations, 37 PVSs and four surgical sperm retrievals. Low ejaculate volume was observed in 33% of the patients, and oligozoospermia in 37% of the patients. Specimens from 77 of the patients contained motile sperm and were therefore frozen for future use. There was no statistical difference for any of the fresh semen parameters between all groups. Twenty of them underwent ICSI leading to five live births, while four underwent intrauterine insemination. ART with frozen-thawed spermatozoa can provide men with SCI with comparable results as in the infertile population.

[Ovarian hyperstimulation syndrome after stimulation with highly purified hMGfor in vitro fertilization: Observational study SHOview]. / Le syndrome d'hyperstimulation ovarienne après stimulation par hMG hautement purifiée dans le cadre de la fécondation in vitro : étude observationnelle SHOview.

OBJECTIVE: Data on the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in France are limited. METHODS: Prospective observational multicentric study (23 French centers of IVF) in a cohort of 421 women treated with highly purified hMG (HP-hMG) for the first or second cycle of IVF with or without ICSI. The primary objective was to assess the incidence of moderate to severe OHSS in this cohort. RESULTS: At inclusion, 172 patients (40.9%) were considered at risk of OHSS by the physicians. The main measures for risk minimization taken by the physicians rested on initial dose of HP-hMG and protocol choice. At the end of the follow-up (4 months in average), the rate of OHSS moderate to severe was 2.4% (confidence interval 95%: 1.1-4.3%) for the studied IVF cycle. OHSS was severe for 3 women (0.7%) and moderate for 7 women (1.7%). CONCLUSION: This rate of OHSS after IVF is at the lower limit of the rates reported in the literature for OHSS. This study brings reassuring epidemiological data on the rate of OHSS in women at risk. The measures taken by the physicians to minimize the risk of OHSS could have contributed to this low incidence.

Prospective evaluation of serum anti-Müllerian hormone dynamics in 250 women of reproductive age treated with chemotherapy for breast cancer.

AIM: Women of reproductive age with breast cancer generally receive gonadotoxic chemotherapy. Fertility issues are of great concern for them. However, little is known on ovarian damage during chemotherapy and its evolution during long-term follow-up. The aim of this study was to provide a detailed description of serum anti-Müllerian hormone (AMH) evolution during chemotherapy and 24-month follow-up. METHODS: This prospective cohort study was conducted in 250 patients, aged 18-39 years, diagnosed with breast cancer and treated with adjuvant/neoadjuvant chemotherapy. Each patient underwent blood AMH measurement at each chemotherapy cycle, and at 6, 12 and 24 months after chemotherapy. Menses occurrence was also recorded. RESULTS: Mean basal AMH level was 4.19 ± 4.84 ng/mL, and was negatively correlated with age. Serum AMH level rapidly decreased in all patients after each chemotherapy cycle to undetectable levels in most of them, and slowly increased in 45% of the patients during the 24-month follow-up. AMH decrease was significantly associated with age and basal AMH level, but not with cyclophosphamide dose and tamoxifen use. The prevalence of chemotherapy-related amenorrhoea was 92.4% at the end of chemotherapy; women with amenorrhoea being significantly older and having lower basal AMH than women who resumed menses. CONCLUSIONS: Our study confirms rapid and deep ovarian reserve alteration in young women receiving chemotherapy for breast cancer, and shows moderate AMH recovery in some patients. Although AMH cannot alone predict fertility potential, these new data emphasise the need for post-treatment ovarian insufficiency follow-up, strongly support the use of fertility preservation strategies and may provide new tools for improved counselling.

Anti-müllerian hormone levels and evolution in women of reproductive age with breast cancer treated with chemotherapy.

BACKGROUND: Long-term consequences of cancer treatments in young women, and especially fertility issues, are gaining attention as survival rates increase. Breast cancer is the most frequent malignancy in women of reproductive age. AIM: The purpose of this review is to describe serum anti-müllerian hormone (AMH) level at diagnosis and its evolution during and after chemotherapy in women of reproductive age treated for breast cancer. Second, the impact of taxanes on AMH, the association between AMH and amenorrhea, and the comparison of AMH with other hormonal markers of ovarian reserve were studied. METHODS: A systematic PubMed search was conducted on all articles, published up to April 2016 and related to AMH in women suffering from breast cancer using the following key words: AMH, müllerian-inhibiting substance, ovarian reserve, ovarian function, breast cancer, gonadotoxicity, ovarian toxicity, amenorrhea, chemotherapy, and menopause. RESULTS: AMH levels rapidly fall down to undetectable levels in most women during chemotherapy and generally persist at very low levels in most women after the treatment. Taxanes seem to impact negatively ovarian function, but data on ovarian reserve are scarce. AMH is a predictor of the occurrence of chemotherapy-related amenorrhea and is the most relevant hormonal marker of ovarian reserve. CONCLUSION: Serum AMH is a relevant tool for ovarian reserve assessment and follow-up during treatment in premenopausal women with breast cancer. Further large prospective studies are necessary to determine its predictive interest for post-treatment residual fertility, and eventually use it in fertility preservation counseling before treatment initiation.

[High doses of gonadotropins for controlled ovarian hyperstimulation: A case-control study]. / Stimulation ovarienne à fortes doses de gonadotrophines en FIV : étude rétrospective cas-témoin au CHU de Nantes.

OBJECTIVES: While assisted reproductive technology (ART) activity increases throughout the world, most teams have to face with the challenge of ovarian stimulation in poor responders. Despite a huge amount of literature available, no consensus currently exists on the best protocol, molecule or dose to use in these patients. The main objective of this case-control study was to compare ovarian stimulation and IVF outcome in patients at risk of poor ovarian response undergoing antagonist protocol with high doses of gonadotropins (≥450IU/day) versus patients undergoing stimulation at 300IU/day. METHODS: This retrospective monocentric study was conducted in 2013 on antagonist cycles performed with ≥450IU/day. Each cycle was matched with a control antagonist cycle with 300IU/day injection, with strict matching for ART type, age, serum anti-müllerian hormone (AMH) and body mass index (BMI). RESULTS: A total of 82 high dose cycles were matched and compared with 82 control cycles. Both groups were comparable, except for poor responder prevalence and mean IVF rank, which were higher in high dose group than in control group. No significant difference was observed between the groups in terms of number of oocytes, embryos, fertilization rate, implantation and ongoing pregnancy rates. CONCLUSIONS: No ovarian stimulation protocol has demonstrated its superiority in expected poor responders up to now, especially regarding doses of gonadotropins to use. Accordingly, our study did not show any difference between high dose stimulation regimen (≥450IU/day) and conventional stimulation (300IU/day) in terms of IVF cycle outcome.

Leptin and its potential interest in assisted reproduction cycles.

BACKGROUND: Leptin, an adipose hormone, has been shown to control energy homeostasis and food intake, and exert many actions on female reproductive function. Consequently, this adipokine is a pivotal factor in studies conducted on animal models and humans to decipher the mechanisms behind the infertility often observed in obese women. METHODS: A systematic PubMed search was conducted on all articles, published up to January 2015 and related to leptin and its actions on energy balance and reproduction, using the following key words: leptin, reproduction, infertility, IVF and controlled ovarian stimulation. The available literature was reviewed in order to provide an overview of the current knowledge on the physiological roles of leptin, its involvement in female reproductive function and its potential interest as a prognostic marker in IVF cycles. RESULTS: Animal and human studies show that leptin communicates nutritional status to the central nervous system and emerging evidence has demonstrated that leptin is involved in the control of reproductive functions by acting both directly on the ovaries and indirectly on the central nervous system. With respect to the clinical use of leptin as a biomarker in IVF cycles, a systematic review of the literature suggested its potential interest as a predictor of IVF outcome, as high serum and/or follicular fluid leptin concentrations have correlated negatively with cycle outcome. However, these preliminary results remain to be confirmed. CONCLUSION: Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered. Preliminary studies evaluating leptin as a biomarker in human IVF seem promising but need further confirmation.

[Fertilization failure in IVF and ICSI]. / Les échecs de fécondation en FIV et en ICSI.

OBJECTIVES: To assess male and female clinical and biological parameters that may explain fertilization failure in vitro fertilization (IVF) and IVF with intra-cytoplasmic sperm injection (ICSI). MATERIAL AND METHODS: Retrospective case-control study including 1282 IVF or ICSI cycles at the centre hospitalier universitaire of Nantes from September 2010 to February 2012. The "Fertilization Failure" group, showing no sign of fertilization, has been compared with the "Control patients" group, getting at least one embryo. RESULTS: Several significant differences were noted as, in the "Fertilization Failure" group, lower values of antral follicles (P<0.05), of inseminated oocytes (P<0.001) and active sperm (P<0.001) in IVF, and a lower quantity and quality of oocytes (P<0.001) in ICSI. The correlation tests have confirmed a significant association with these parameters. However, the logistic regression tests did not identify explanatory or predictive factor in IVF or ICSI. CONCLUSION: In our study, in accordance with literature data, impaired sperm parameters were mainly involved in complete fertilization failure in IVF, and a lower oocyte quality in ICSI.

Double-blind prospective study comparing two automated sperm analyzers versus manual semen assessment.

PURPOSE: Despite controversy regarding its clinical value, male fertility investigation mainly relies on semen analysis. Even though reference guidelines are available, manual sperm analysis still suffers from analytical variability, thus questioning the interest of automated sperm analysis systems. The aim of this study is to compared automated computerized semen analysis systems (SQA-V GOLD and CASA CEROS) to the conventional manual method in terms of accuracy and precision. METHODS: We included 250 men in this double-blind prospective study. The SQA-V GOLD (Medical Electronic Systems) and CEROS, CASA system (Hamilton Thorne) were compared to the standard manual assessment based on the WHO 5th Edition. The main outcome measures were sperm concentration, total sperm number, total motility, progressive motility, non-progressive motility, morphology, motile sperm concentration (MSC) and progressively motile sperm concentration (PMSC) with the three methods. RESULTS: Statistical analysis of the test results from the automated systems and the manual method demonstrated no significant differences for most of the semen parameters. The Spearman coefficients of rank correlation (rho) for CASA and the SQA-V GOLD automated systems vs. the manual method were: Sperm concentration (0.95 and 0.95), total sperm number (0.95 and 0.95), MSC (0.94 and 0.96) and PMSC (0.94 and 0.93) correspondingly. Concerning sperm morphology, both automated systems demonstrated high specificity (Sp) and negative predictive values (NPV), despite significantly different medians (CASA: 83.7 % for Sp and 95.2 % for NPV, SQA-V: 97.9 % for Sp and 92.5 %). The highest precision (lowest 95 % confidence interval for duplicate tests) for all semen variables was found in the SQA-V GOLD. CONCLUSIONS: The advantages of using automated semen analysers are: Standardization, speed (lower turnaround time), precision, reduced potential for human error, automated data recording and less need for highly skilled professionals to run the systems. The disadvantages of using automated systems are: notably the problem with testing some atypical samples and the inability to perform an assessment of morphology abnormalities. Based on the results of this study, the SQA-V Gold demonstrated better agreement vs. the manual method. In conclusion, automated semen analyzers can be used for routine semen analysis providing rapid clinically acceptable results with higher precision, and positively impacting laboratory standardization.

[Interest of systematic syphilis serology testing prior to assisted reproductive technology cycles: a retrospective study in Nantes, France]. / Quel intérêt pour la réalisation systématique de la sérologie syphilis avant AMP ? Étude rétrospective au CHU de Nantes de 2000 à 2010.

INTRODUCTION: Syphilis has recently re-emerged in young adults. However, serological testing of patients undergoing assisted reproductive technology (ART) cycles and/or semen cryopreservation is not mandatory in every country. PATIENTS AND METHOD: We conducted a retrospective analysis on our local database to evaluate the prevalence of syphilis among infertile couples, and discuss the interest of systematic syphilis serology testing in these patients. RESULTS: Between 2000 and 2010, only one patient out of 4314 was diagnosed with chronic syphilis. CONCLUSION: This study illustrates that systematic serological screening for syphilis in couples referred for semen cryopreservation or ART only allows exceptionally rare diagnosis. The cost-effectiveness of this strategy should be reconsidered.

Comparative proteomic analysis coupled with conventional protein assay as a strategy to identify predictors of successful testicular sperm extraction in patients with non-obstructive azoospermia.

Among infertile couples, approximately half have to face with male infertility. In men with non-obstructive azoospermia, surgical retrieval testicular sperm extraction (TESE) of spermatozoa can be attempted, but with low success rates. A specific biomarker that could predict residual spermatogenesis would obviously be of interest before performing TESE. Thus, our aim was to identify biomarkers of residual spermatogenesis in seminal plasma of patients with non-obstructive azoospermia (NOA) using an isotope-coded protein label (ICPL)-based proteomic strategy coupled with conventional protein assay. This retrospective study was conducted in 40 men with NOA at the University Hospital of Nantes and Proteomics Core facility Biogenouest - Inserm U1085 - IRSET, Rennes, France. Comparative ICPL proteomic screening of frozen seminal plasma and correlation with TESE outcome allowed the identification of some differentially expressed proteins. Among them, lectin galactoside-binding, soluble 3 binding protein (LGALS3BP) expression was further confirmed using conventional protein assay, and its interest as a predictor of TESE outcome was then evaluated and compared with conventional clinical and hormonal markers of residual spermatogenesis. Among the 12 differentially expressed proteins identified with comparative ICPL proteomic strategy, seminal LGALS3BP expression was found to be significantly higher in men with successful TESE. Finally, comparative ICPL proteomic screening of seminal plasma appears to be a promising approach for the identification of biomarkers of residual spermatogenesis. LGALS3BP, associated with clinical and hormonal markers, could potentially be used as a predictive marker of successful TESE outcome in patients with NOA.

Canine-chilled sperm: study of a semen extender made with low-density lipoproteins from hen egg yolk supplemented with glutamine.

The objective of this study was to evaluate the effects of a combination of 6% low-density lipoproteins (LDL) and 20 mm glutamine in comparison with other extenders used for the refrigeration of canine semen: Tris egg yolk (EY) 20% and 6% LDL. The percentages of mobile spermatozoa after 4 days storage in a domestic refrigerator at +4 °C were 53.1%, 44.2% and 52.2% for the 6% LDL + 20 mm glutamine, 20% EY and 6% LDL extenders respectively for 100% of the dogs. After 7 days of storage, these percentages fell to 37.8%, 26.4% and 33.6% in the same extenders for 50% of the dogs. In vitro fertility tests were performed with all of the extenders following the mobility results. These tests were conducted on the day of sampling (D0), and 48 and 96 h after sampling. The results of the hypo-osmotic swelling test were 82.6%, 81.2% and 85.7% on D0, 75.2%, 74.1% and 78.5% on D2, and 70.8%, 71% and 76.1% on D4 for the 6% LDL + 20 mm glutamine, 20% EY and 6% LDL extenders, respectively. For the FITC/pisum sativum agglutinin (PSA) test, the results were 81.5%, 70.2% and 84.8% on D0, 78.9%, 62.3% and 84.2% on D2, and 72.7%, 59.6% and 73.7% on D4 for the 6% LDL + 20 mm glutamine, 20% EY and 6% LDL extenders, respectively. The acridine orange test was positive; in nearly 100% of cases, none of the spermatozoa had been denatured on D0, D2 and D4. The 6% LDL + 20 mm glutamine and the 6% LDL extenders are capable of preserving spermatozoa that have been stored in a domestic refrigerator at +4°C for at least 4 days. This means that the spermatozoa retain good cytoplasmic membrane integrity, had not capacitated and contained intact DNA in comparison with spermatozoa preserved in the egg yolk extender. The duration of storage is a very important consideration when faced with the problem of sending semen over ever-greater distances.

[Ovarian cryopreservation: what future?]. / La congélation ovarienne: quel avenir?

Ovarian cortex cryobanking is a technique of fertility preservation that led to the birth of about 20 children in the world since 2004. Its main limitations are low follicular survival rate after thawing and transplantation and the risk of disease reintroduction. A lot of research is currently conducted in order to optimize both efficacy and safety of the graft and to develop alternative techniques to restore fertility. These advances will allow oncologists to offer this technique to a growing number of patients in the context of fertility preservation (for medical or social indications), but also in other indications such as puberty induction or menopause treatment.

[Time lapse (Embryoscope®) as a routine technique in the IVF laboratory: a useful tool for better embryo selection?]. / L'observation en continu du développement embryonnaire en FIV (time lapse) à l'aide de l'Embryoscope(®) : un outil d'aide à la décision ?

Among all the strategies available in order to improve success rates in IVF cycles, a lot of work has been done on embryo culture conditions and embryo quality evaluation. Most IVF centres use conventional incubators and select embryo according to punctual morphological evaluation, but this strategy has several limitations. Recently developed commercial devices associating more stable culture conditions and time lapse observation of embryo development provide new insights into early embryo development in IVF cycles. Among them, the Embryoscope(®) appears to be the most user-friendly, performing and suited for routine daily practice. The first Embryoscope(®) for France was installed in the University Hospital of Nantes in 2011. In our experience, it takes relatively a short time to get used to this system. Moreover, its integration in routine process yielded several advantages, such as better embryo selection according to kinetic parameters and observation of abnormal cleavage events, continuing education and training, quality control and flexibility. This leaded to an overall increase in success rates in IVF cycles.

[Modified Risdon approach for non-traumatic ramus surgery]. / La voie d'abord sous-angulo-mandibulaire en dehors de la traumatologie.

INTRODUCTION: The Risdon modified approach, for mandibular surgery, is well adapted to treatment of low subcondylar fractures. According to our experience, this approach with a low rate of complications should also be considered for non-traumatic ramus surgery. MATERIAL AND METHODS: Twenty Risdon modified approaches were used in 11 patients for non-traumatic indications (seven bilateral osteotomies, four unilateral osteotomies, one biopsy, one bone graft). One patient was operated twice with the same approach. RESULTS: In all cases, the planned surgery could be performed using this approach. The only complication was a case of temporary paresis of the facial nerve's mandibular branch. The scar was always considered as quite acceptable. DISCUSSION: As for traumatology, the Risdon modified approach is an improvement for ramus non-traumatic surgery. It has a very low rate of complications, especially for the facial nerve. The intraoral approach avoids scarring, but the resulting exposure is insufficient and requires using a transcutaneous device or endoscopy. In orthognathic surgery, the wide exposure of the lateral aspect of the ramus, the corpus, and the basilar edge, facilitates important mandibular advancement.