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.

Total blastocyst usable rate is a predictor of cumulative live birth rate in IVF cycles.

PURPOSE: Despite advances in IVF techniques, determining the prognostic factors influencing cumulative live birth rate (CLBR) remains crucial for optimizing outcomes. Among the various key performance indicators in the lab, blastulation rate, and more specifically Total Blastocyst Usable Rate (TBUR), has gained particular interest. In this study we aimed at determining if TBUR was significantly associated with CLBR. BASIC PROCEDURES: This monocentric retrospective case-control study was conducted in 317 consecutive IVF/ICSI cycles in 2014-2020 and leading to the formation of 3 usable blastocysts, including freeze all cycles. TBUR (usable blastocysts / 2PNs) was calculated and CLBR after 2-year follow up was recorded, including both fresh and frozen embyro transfers. CLBR was then compared between 2 groups according to TBUR (group 1: TBUR ≥50 % vs group 2: TBUR ≤30 %). MAIN FINDINGS: CLBR was significantly higher in group 1 than in group 2 (57 vs. 41 %, p = 0.02). Adjusted logistic regression showed a statistically significant relationship between CLBR and TBUR, with a significantly lower chance of achieving a live birth in group 2 than in group 1 (OR = 0.408 [0.17-0.96]; p = 0.04). PRINCIPAL CONCLUSIONS: Although the monocentric design and the arbitrary choice of thresholds for TBUR and number of blastocysts call for caution when generalizing the findings and advocates for external validation, our results illustrate that TBUR is a valuable prognostic factor of CLBR in IVF cycles which might serve as a tool for lab monitoring, cycle analysis by medical staff and patients' counselling. These results fit well within the P4 medicine concept (Predictive, Preventive, Personalized, and Participatory), and advocate for further research in order to improve embryo culture conditions.

Female smoking does not affect live birth rate after frozen thawed blastocyst transfer cycle.

PURPOSE: The development of vitrification and blastocyst culture have recently led to a rapidly growing number of single frozen thawed blastocyst transfer (FBT) cycles worldwide. Although the impact of female smoking on spontaneous fertility is well established, its effect on assisted reproductive technologies (ART) outcome is still controversial, and no study has specifically evaluated its effect on FBT cycles' outcome. METHODS: This retrospective study was conducted in all consecutive FBT cycles conducted between 2012 and 2021 in a single University-based ART centre. Endometrial preparation was standard and based on hormonal replacement therapy. One or two blastocysts were transferred according to couple's history and embryo quality. Female smoking status was recorded for each cycle, and the association between female smoking status and Live Birth Rate (LBR) after FBT cycle was evaluated with univariate and multivariate analysis. RESULTS: A total of 1537 FBT cycles performed in non-smoking women and 397 FBT cycles performed in smoking women were included in the analysis. No independent association between female smoking status and LBR in FBT cycles was found after logistic regression (OR=1.07 [0.79-1.45], p = 0.649). CONCLUSION: Our study suggests that female smoking might not impair endometrial receptiveness in non-stimulated FBT cycles. Further studies should nevertheless consider assessing more precisely the current smoking exposure.

[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.

[Fertility preservation and access to medically assisted reproduction for Trans people: Guidelines from French Professional Association for Transgender Health]. / Préservation de la fertilité et accès à l'assistance médicale à la procréation chez les personnes Trans : recommandations de Trans Santé France.

Many health care professionals are dealing with the issue of transgender people in their medical practice. In the field of reproduction, Trans people can benefit from fertility preservation before the introduction of hormonal treatment or surgery altering their fertility. This article, which is the result of a collaborative work of several reproductive professionals involved in the health of Trans people, provides an overview of the possibilities of fertility preservation and medically assisted reproduction techniques in France for Trans people.

[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.

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.

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.

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.

Gastric involvement in juvenile polyposis associated with germline SMAD4 mutations: an entity characterized by a mixed hypertrophic and polypoid gastropathy.

Exclusively gastric form of juvenile polyposis associated with germline SMAD4 mutation is a rare clinical entity and is usually difficult to diagnose in the absence of colorectal lesions. We describe the phenotype of two unrelated cases of exclusive or predominant gastric expression of juvenile polyposis. Endoscopically, we found an unusual hypertrophic and polypoid gastropathy with abundant mucus adhering to the mucosal surface. Initially diagnosed as hyperplastic polyps, examination of gastric macrobiopsy specimens and identification of SMAD4 gene mutation in both cases confirmed the diagnosis. Close upper GI surveillance was proposed in case 1 and prophylactic total gastrectomy in the second one. Juvenile polyposis limited to the stomach is a rare condition that is linked to SMAD4 mutations. Such a diagnosis should be considered whenever a mixed, hypertrophic and polypoid gastropathy is encountered.

[Controlled study of outcome after 6 months to early intervention of bus driver victims of aggression]. / Etude contrôlée sur l'efficacité à 6 mois d'une prise en charge précoce de 132 conducteurs d'autobus victimes d'agression.

The aftermath of psychological trauma, long since studied in the context of war ("soldier's heart", "shell shock", etc.) can also occur as a result of trauma in civilian life. Bus drivers in large urban area are frequently aggressed. Over a period of 5 months, bus drivers who had been aggressed, employees of the largest French urban transport company (RATP), participated in a study designed to evaluate the effects of cognitive behavior treatment provided shortly after such aggression. A total of 132 bus drivers were included in the study divided into 2 randomized groups: a control group (67 subjects) received the usual medical-social care offered by the company, and a treatment group (65 subjects) who, in addition, benefited from 1 to 6 sessions of cognitive behavior intervention, including:evocation of the aggression, relaxation, role plays, cognitive restructuring. Subjects were evaluated by self-questionnaires a few days post-aggression and re-evaluated 6 months later. At follow-up, results showed a statistically significant decrease in anxiety levels (measured by the HAD scale) and intrusion of the traumatic memory (as evaluated by the Horowitz scale) in the treatment group. Hence, early and structured intervention appears to lessen the impact of the traumatic event on bus drivers attacked at work.

[Does manometric megarectum have a symptomatic role in patients complaining of dyschezia?]. / Le mégarectum manométrique a-t-il une responsabilité symptomatique chez les patients se plaignant d'une dyschésie?

UNLABELLED: Adults with dyschezia are occasionally diagnosed as having megarectum when anorectal manometry identifies rectal sensory disturbances. It remains difficult however to ascertain whether this state represents a part of the pathophysiological process responsible for symptoms, or just an associated phenomenon. The aim of this study was to highlight the symptomatic and functional features encountered in patients with dyschezia and megarectum, and to compare them with those obtained in an asymptomatic group and in a group of patients complaining of dyschezia without manometric megarectum. PATIENTS AND METHODS: The maximum tolerable volume (MTV) was defined as the highest tolerable volume which induced painful and irrepressible repletion upon inflation of the rectum with air. The upper normal range of MTV (330 mL) was obtained from rectal manometry performed in a group of 18 healthy volunteers and asymptomatic patients (mean age: 37.8 +/- 14 years, 12 F, 6 M). Between February 90 and February 92, 27 consecutive adults (48 ans +/- 15 years, 26 F, 1 M) suffering from dyschezia were found to have abnormally increased MTV, and were compared to a group of 35 patients (47 +/- 15.3 years, 34 F, 1 M) with dyschezia with MTV within normal ranges. Symptomatic patients underwent detailed interrogation, clinical examination, anorectal manometry, and evacuation proctography. RESULTS: Parity, prevalence of hysterectomy, symptoms and natural history did not differ between the two groups except for increased use of antidepressive agents in the megarectum group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Remission of Lambert-Eaton syndrome over a 10-year period. Recurrence without evidence of tumor at autopsy]. / Rémission d'un syndrome de Lambert-Eaton pendant 10 ans. Récidive sans tumeur décelable a l'autopsie.

A case of Lambert-Eaton's syndrome with onset 18 months prior to detection of an epidermoid cancer of the larynx is reported. Regression of the syndrome, and its total remission over 10 years without treatment following excision of the tumor, suggested a possible relationship as a paraneoplastic disorder. However, doubt was cast on any possible link by recurrence of the Lambert-Eaton's syndrome after 10 years remission, and the satisfactory course without treatment over the next 6 years combined with failure to detect any tumor recurrence or metastases, even at autopsy. The question raised is whether this is indeed a true paraneoplastic affection or a fortuitous association of an idiopathic form of Lambert-Eaton's syndrome and an infrequent cancer which, in addition, has never been reported at the origin of the Lambert-Eaton syndrome.

[Involvement of the central nervous system in Behçet's syndrome. Report of two cases (author's transl)]. / L'atteinte du système nerveux central au cours de la maladie de Behçet. A propos de deux observations.

After presenting two personal observations, the authors underline the fact that the neurological manifestations of Behçet's disease are more frequent than they were supposed to be. Their symptoms are overly manifold but have in common constant abnormality in the cerebrospinal fluid when an attack occurs. The affection is a very serious one demanding an early and well established diagnosis only to be obtained thanks to a clinical examination. Corticosteroïd therapy (1 mg/kg per day) either alone or associated with immuno-suppressive therapy may check the attack. Preventing relapses implies a non-stop treatment. Immuno-suppressive therapy seems to be the most efficient one.

[Iatrogenic arthritis after intestinal by-pass as a treatment for obesity (author's transl)]. / Les polyarthralgies en rapport avec les dérivations intestinales.

The authors report three observations of patients having suffered from arthralgias as an aftermath of intestinal by-pass for treatment of refractory obesity. They remind the main troubles cropping up after such surgical treatment and refer to the data already existing in the literature dealing with articular manifestations. They think this pathology is in keeping with arthritis already reported in inflammatory colitis and they suggest a similar pathogeny.