Adaptive data-driven models to best predict the likelihood of live birth as the IVF cycle moves on and for each embryo transfer.

PURPOSE: To dynamically assess the evolution of live birth predictive factors' impact throughout the in vitro fertilization (IVF) process, for each fresh and subsequent frozen embryo transfers. METHODS: In this multicentric study, data from 13,574 fresh IVF cycles and 6,770 subsequent frozen embryo transfers were retrospectively analyzed. Fifty-seven descriptive parameters were included and split into four categories: (1) demographic (couple's baseline characteristics), (2) ovarian stimulation, (3) laboratory data, and (4) embryo transfer (fresh and frozen). All these parameters were used to develop four successive predictive models with the outcome being a live birth event. RESULTS: Eight parameters were predictive of live birth in the first step after the first consultation, 9 in the second step after the stimulation, 11 in the third step with laboratory data, and 13 in the 4th step at the transfer stage. The predictive performance of the models increased at each step. Certain parameters remained predictive in all 4 models while others were predictive only in the first models and no longer in the subsequent ones when including new parameters. Moreover, some parameters were predictive in fresh transfers but not in frozen transfers. CONCLUSION: This work evaluates the chances of live birth for each embryo transfer individually and not the cumulative outcome after multiple IVF attempts. The different predictive models allow to determine which parameters should be taken into account or not at each step of an IVF cycle, and especially at the time of each embryo transfer, fresh or frozen.

A real-world study of ART in France (REOLA) comparing a biosimilar rFSH against the originator according to rFSH starting dose.

BACKGROUND: Since the first launch of a biosimilar recombinant follicle stimulating hormone (rFSH), Bemfola®, in Europe in 2014, it has been possible to study in routine clinical care throughout France the effectiveness of a biosimilar rFSH including according to different rFSH starting doses. METHODS: REOLA was a non-interventional, retrospective, real world study using anonymized data from 17 Assisted Reproductive Technology (ART) centres' data management systems across France including 2,319 ART ovarian stimulation cycles with Bemfola® and 4,287 ART ovarian stimulation cycles with Gonal-f®. For both products, four populations were studied according to starting dose of rFSH: < 150 IU, 150 - 224 IU, 225 - 299 IU and ≥ 300 IU. The primary endpoint was the cumulative live birth rate (cLBR) per commenced ART ovarian stimulation cycle including all subsequent fresh and frozen-thawed embryo transfers starting during a follow up period of at least 1 year following oocyte retrieval. RESULTS: A direct relationship of increasing rFSH starting dose with increasing age, increasing basal FSH, decreasing AMH and increasing body mass index was noted. No clinically relevant differences were seen in all outcomes reported, including the cLBR, between Bemfola® and Gonal-f®, but for both drugs, an association was seen with increasing rFSH starting dose and decreasing cLBR. CONCLUSIONS: The REOLA study demonstrates that the cLBR with Bemfola® is very similar to Gonal-f® across all patient subpopulations. The cLBR is inversely related to the rFSH starting dose irrespective of the drug used, and the REOLA study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting.

Added value of anti-Müllerian hormone serum concentration in assisted reproduction clinical practice using highly purified human menopausal gonadotropin (HP-hMG).

INTRODUCTION: The individual response to controlled ovarian stimulation (COS) depends on several factors, including the initial dose of gonadotropin. In repeated in vitro fertilization (IVF) cycles, the initial dose of gonadotropin is mainly established on the basis of the previous attempts' outcomes. Conversely, in naive patients, the ovarian response should be estimated using other criteria, such as the serum concentration of anti-Müllerian hormone (AMH). However, in clinical practice, the initial gonadotropin dose is not systematically adapted to the AMH level, despite the known relationship between AMH and ovarian reserve. MATERIAL AND METHODS: French non-interventional, longitudinal, prospective, multicentre, cohort study that included infertile women who underwent COS with highly purified human menopausal gonadotropin (HP-hMG 600 IU/mL) during their first IVF/intracytoplasmic sperm injection (ICSI) cycle. Data were collected prospectively during routine follow-up visits from COS initiation to 10-11 weeks after embryo transfer. RESULTS: Data from 235 of the 297 enrolled women were used for the study. Serum AMH level was negatively correlated with the initial and total HP-hMG doses (p<0.001), and positively correlated with the number of retrieved oocytes (p<0.007). Embryos were obtained for 94.0% of women, and fresh embryo transfer was performed in 72.8% of them. The clinical pregnancy rate was 28.5% after the first embryo transfer. CONCLUSION: Selecting the appropriate starting dose of gonadotropin is crucial to optimize the IVF/ICSI procedure. For the first attempt, the serum AMH level is a good biomarker to individualize treatment.

Patient perceptions and understanding of treatment instructions for ovarian stimulation during infertility treatment.

The impact of patient-physician communication and levels of understanding of treatment on patient knowledge and compliance has been studied in patients undergoing their first cycle of infertility treatment. This observational, real-life, longitudinal study involved 488 patients from 28 infertility centres in France. Data on communication quality, understanding of treatment instructions, patient knowledge and compliance to treatment protocol were collected through questionnaires administered before treatment initiation (V1) and at oocyte retrieval (V2). At V1, patients were very satisfied with their levels of understanding of the injection and monitoring schedules, the information given by the medical team, and the way of receiving instructions, with average ratings on a scale of 0-100% of > 75%. They rated their understanding of possible treatment side-effects as satisfactory (average score 71.1%). Gaps in patient knowledge about their treatment, revealed by discrepancies between physician and patient reports, were observed in 20.5% of patients (n = 79/386), and most commonly resulted from confusion about the units and dose of gonadotropin. Anxiety about performing self-injections and a lack of confidence in their ability to self-inject correctly were each observed in approximately one-third of patients. Patient self-assessment of compliance at V2 revealed that 27% of patients (n = 83/305) did not comply with or had doubts about the injection schedule or dose injected. Meanwhile physicians reported high levels of patient compliance (94.3%; n = 350/371). In conclusion, even when patient-physician relationships appear to be satisfactory, patient miscomprehension and non-compliance during infertility treatment may be underestimated. Further interventions are required to improve these outcomes.

Outbreak of IMI-1 carbapenemase-producing colistin-resistant Enterobacter cloacae on the French island of Mayotte (Indian Ocean).

The spread of carbapenemase-producing Enterobacteriaceae in the Southwest Indian Ocean islands is poorly known. Here we describe an outbreak of colistin-resistant Enterobacter cloacae harbouring blaIMI-1 in the French overseas department of Mayotte. Between October 2015 and January 2017, all isolates of imipenem-non-susceptible E. cloacae at Mayotte Medical Center and University Hospital of Reunion Island were screened for carbapenemase production. Positive isolates were typed by pulsed-field gel electrophoresis and whole-genome sequencing (WGS)-based multilocus sequence typing (MLST), and all ß-lactamase genes were identified by PCR and sequencing. Resistance profiles were determined by agar diffusion and Etest. Genetic support of the blaIMI-1 gene was determined by WGS. A total of 18 E. cloacae isolates harbouring blaIMI-1 were detected in 17 patients from Mayotte. Pulsed-field gel electrophoresis (PFGE) analysis showed 16 of the 18 strains to be clonally related and belonging to ST820. Based on clinical data, this outbreak most likely had a community origin. The blaIMI-1 gene in the 18 isolates was carried by a new variant of an integrative mobile element involving the Xer recombinases, called EcloIMEX-8. The mcr-1-mcr-5 genes were absent from the collection. The isolates belonged to E. cloacae cluster XI, known to be colistin heteroresistant. Here we report the first outbreak of IMI-1-producing Enterobacteriaceae. IMI-1-producers may be underdetected in microbiology laboratories because of their unusual antimicrobial resistance profile (resistant to imipenem but with intermediate resistance to ertapenem and susceptible to extended-spectrum cephalosporins) and the absence of blaIMI-1 in the panel of genes targeted by molecular diagnostic kits.

A computerized decision support system for ovarian stimulation by gonadotropins.

OBJECTIVE: To evaluate the effectiveness of a computerized decision support system for ovarian stimulation with gonadotropins. DESIGN: Retrospective and prospective randomized studies. SETTING: Private and university teaching hospital. PATIENT(S): Women undergoing ovarian stimulation to treat infertility. MAIN OUTCOME MEASURE(S): Pregnancy rate. RESULT(S): In the retrospective study, computer-generated decisions were compared with clinicians' decisions in 118 stimulated cycles in 53 patients. In 90% of cases, the choice of FSH regimens and adjustments to dosages were identical. In the prospective study, the computer-generated decisions achieved a pregnancy rate per cycle of 18% (15 of 82 cycles), compared with 16% (13 of 82 cycles) achieved by clinicians. CONCLUSION(S): A computerized decision making system was as effective as skilled clinicians in achieving pregnancy by using ovarian stimulation with FSH.