[First-line management of infertile couple. Guidelines for clinical practice of the French College of Obstetricians and Gynecologists 2022]. / Prise en charge de première intention du couple infertile : mise à jour des RPC 2010 du CNGOF.

OBJECTIVE: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples. MATERIALS AND METHODS: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts. RESULTS: The fertility work-up is recommended to be prescribed according to the woman's age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple's initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery. CONCLUSION: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

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 multi-centre international study of salivary hormone oestradiol and progesterone measurements in ART monitoring.

RESEARCH QUESTION: Ovarian stimulation during IVF cycles involves close monitoring of oestradiol, progesterone and ultrasound measurements of follicle growth. In contrast to blood draws, sampling saliva is less invasive. Here, a blind validation is presented of a novel saliva-based oestradiol and progesterone assay carried out in samples collected in independent IVF clinics. DESIGN: Concurrent serum and saliva samples were collected from 324 patients at six large independent IVF laboratories. Saliva samples were frozen and run blinded. A further 18 patients had samples collected more frequently around the time of HCG trigger. Saliva samples were analysed using an immunoassay developed with Salimetrics LLC. RESULTS: In total, 652 pairs of saliva and serum oestradiol were evaluated, with correlation coefficients ranging from 0.68 to 0.91. In the European clinics, a further 237 of saliva and serum progesterone samples were evaluated; however, the correlations were generally poorer, ranging from -0.02 to 0.22. In the patients collected more frequently, five out of 18 patients (27.8%) showed an immediate decrease in oestradiol after trigger. When progesterone samples were assessed after trigger, eight out of 18 (44.4%) showed a continued rise. CONCLUSIONS: Salivary oestradiol hormone testing correlates well to serum-based assessment, whereas progesterone values, around the time of trigger, are not consistent from patient to patient.

Day 5 versus Day 6 blastocyst transfers: a systematic review and meta-analysis of clinical outcomes.

STUDY QUESTION: Is there a difference in clinical pregnancy and live birth rates (LBRs) between blastocysts developing on Day 5 (D5) and blastocysts developing on Day 6 (D6) following fresh and frozen transfers? SUMMARY ANSWER: D5 blastocyst transfers (BTs) present higher clinical pregnancy and LBRs than D6 in both fresh and frozen transfers. WHAT IS KNOWN ALREADY: BT is increasingly popular in assisted reproductive technology (ART) centers today. To our knowledge, no meta-analysis has focused on clinical outcomes in both fresh and frozen BT. Concerning frozen blastocysts, one meta-analysis in 2010 found no significant difference in pregnancy outcomes between D5 and D6 BT. Since then, ART practices have evolved particularly with the wide use of vitrification, and more articles comparing D5 and D6 BT cycles have been published and described conflicting results. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis of published controlled studies. Searches were conducted from 2005 to February 2018 on MEDLINE and Cochrane Library and from 2005 to May 2017 on EMBASE, Eudract and clinicaltrials.gov, using the following search terms: blastocyst, Day 5, Day 6, pregnancy, implantation, live birth and embryo transfer (ET). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 47 full-text articles were preselected from 808 references, based on title and abstract and assessed utilizing the Newcastle-Ottowa Quality Assessment Scales. Study selection and data extraction were carried out by two independent reviewers according to Cochrane methods. Random-effect meta-analysis was performed on all data (overall analysis) followed by subgroup analysis (fresh, vitrified/warmed, slow frozen/thawed). MAIN RESULTS AND THE ROLE OF CHANCE: Data from 29 relevant articles were extracted and integrated in the meta-analysis. Meta-analysis of the 23 studies that reported clinical pregnancy rate (CPR) as an outcome, including overall fresh and/or frozen ET cycles, showed a significantly higher CPR following D5 ET compared with D6 ET (risk ratio (RR) = 1.27, 95% CI: 1.15-1.39, P < 0.001). For CPR, calculated subgroup RRs were 2.38 (95% CI: 1.74-3.24, P < 0.001) for fresh BT; 1.27 (95% CI: 1.16-1.39, P < 0.001) for vitrified/warmed BT; and 1.15 (95% CI: 0.93-1.41, P = 0.20) for slow frozen/thawed BT. LBR was also significantly higher after D5 BT (overall RR = 1.50 (95% CI: 1.32-1.69), P < 0.001). The LBR calculated RRs for subgroups were 1.74 (95% CI: 1.37-2.20, P < 0.001) for fresh BT; 1.38 (95% CI: 1.23-1.56, P < 0.001) for vitrified/warmed BT; and 1.44 (95% CI: 0.70-2.96, P = 0.32) for slow frozen/thawed BT. Sensitivity analysis led to similar results and conclusions: CPR and LBR were significantly higher following D5 compared to D6 BT. LIMITATIONS, REASONS FOR CAUTION: The validity of meta-analysis results depends mainly on the quality and the number of the published studies available. Indeed, this meta-analysis included no randomized controlled trial (RCT). Slow frozen/thawed subgroups showed substantial heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS: In regards to the results of this original meta-analysis, ART practitioners should preferably transfer D5 rather than D6 blastocysts in both fresh and frozen cycles. Further RCTs are needed to address the question of whether D6 embryos should be transferred in a fresh or a frozen cycle. STUDY FUNDING/COMPETING INTEREST(S): This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER: CRD42018080151.

Hypertensive pathologies and egg donation pregnancies: Results of a large comparative cohort study.

OBJECTIVE: To determine whether egg donation (ED) pregnancies are at higher risk of pregnancy-induced hypertension (PIH) than those achieved by autologous assisted reproductive technology (ART; controls). DESIGN: Anonymous comparative observational matched cohort study. SETTING: Assisted reproductive technology centers. PATIENT(S): Two hundred seventeen ED and 363 control singleton pregnancies matched at 7-8 weeks (pregnancy date, parity, cycle type [fresh/frozen] and women's age). According to French practice, all women were under 45. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Percentage of PIH for ED versus controls. RESULT(S): The groups were comparable (mean age, 34.5). PIH was more frequent during ED pregnancies (17.8% vs. 5.3%), as was preeclampsia (11.2% vs. 2.8%) and eclampsia (1.8% vs. 0.0%). In multivariate analyses, PIH risk increased with ED (odds ratio [OR], 3.92; 95% confidence interval [CI], 1.93-7.97) and women's age (OR, 1.08; 95% CI, 1.00-1.16). No significant effect of previous pregnancies or cycle rank/type was observed. CONCLUSION(S): This study had sufficient power to detect doubling of the PIH rate. It was demonstrated that the risk of PIH was tripled for ED versus controls. Even in young women, ED is a risk factor for PIH. An immunological explanation seems most likely, that is, the fetus is fully allogeneic to its mother. This risk must be acknowledged to inform couples and provide careful pregnancy monitoring.

[The use of mechanical restraint and seclusion: comparing the clinical practice in Germany and Switzerland]. / Ein Vergleich von Schweizer und deutschen Kliniken in Bezug auf die Anwendung von Fixierung und Isolierung.

OBJECTIVE: Although coercive measures are one of the indicators of the quality of psychiatric in-patient care, reliable and valid data comparing the practice in different countries are not available. Due to the diversity of definitions, types of coercive measures analysed, case/patient mix and indicators calculated, published national results can not be compared. This study intended to standardizedly assess the use of mechanical restraint and seclusion across German and Swiss hospitals. METHODS: The frequency and duration of these coercive measures among patients with ICD-10 F1, F2, F3, F4 and F6 disorders was analysed in seven German and seven Swiss psychiatric hospitals in the year 2004. RESULTS: In Swiss hospitals more cases were exposed to seclusion. In German hospitals more cases were exposed to mechanical restraint. Seclusion as well as mechanical restraint per case were applied more often in German hospitals. Seclusion as well as mechanical restraint were of longer duration in Swiss hospitals. CONCLUSIONS: The results showed different patterns in the use of seclusion and mechanical restraint across Swiss and German hospitals. For future European research, there is a need for uniformed definitions, and reliable documentation of coercive measures and for an identical method of data analysis.

The use of mechanical restraint and seclusion in patients with schizophrenia: a comparison of the practice in Germany and Switzerland.

BACKGROUND: The use of coercive measures is an indicator of the quality of psychiatric inpatient treatment. To date, there is no data available to European comparisons on the incidence of such measures. METHODS: The frequency and duration of mechanical restraint and seclusion on patients with a diagnosis of F2 ICD-10 was analysed in seven German and seven Swiss psychiatric hospitals in the year 2004 using three indicators. Differences between German and Swiss hospitals regarding the indicators were tested for statistical significance using Mann-Whitney-U-tests. RESULTS: 6.6 % (Switzerland) and 10.4 % (Germany) of admissions respectively were affected by mechanical restraint and 17.8 % (Switzerland) and 7.8 % (Germany) respectively by seclusion. Seclusion as well as mechanical restraint per case were applied significantly more often in German than in Swiss hospitals and were of significantly longer duration in Swiss than in German hospitals. CONCLUSION: The results showed different patterns in the use of seclusion and mechanical restraint across Swiss and German hospitals. For future European research on the use of compulsory measures in routine psychiatric care, there is a need for uniformed definitions, reliable documentation of coercive measures as well as for an identical way of data analysis. To meet these conditions is the first step to achieve European standards for the use of coercive measures.

[Incidence of coercive measures as an indicator of quality in psychiatric hospitals. Problems of data recording and processing, preliminary results of a benchmarking study]. / Die Inzidenz von Zwangsmassnahmen als Qualitätsindikator in psychiatrischen Kliniken. Probleme der Datenerfassung und -verarbeitung und erste Ergebnisse.

OBJECTIVE: The clinical practice concerning the use of coercive measures in psychiatry should be compared. METHOD: A common documentation of physical restraint, seclusion, and medication by coercion was introduced among 10 hospitals. RESULTS: 8.4 % of cases treated within the first 6 months of 2004 were exposed to coercive measures with the highest percentage among patients with psychoorganic disorders (32.1 %). The incidence of coercive measures varied highly between different diagnostic groups and hospitals. DISCUSSION: The processing of the large multi-site data sets yields considerable technical problems. Data interpretation should consider confounding factors such as case mix and hospital structure characteristics.

Diagnosis-related frequency of compulsory measures in 10 German psychiatric hospitals and correlates with hospital characteristics.

OBJECTIVE: To investigate the incidence of coercive measures in standard psychiatric care in different psychiatric hospitals. METHODS: We developed a common documentation of mechanical restraint, seclusion, and medication by coercion, and introduced it in 10 participating hospitals. We developed software able to process the data and to calculate four key indicators for routine clinical use. RESULTS: 9.5% of 36,690 cases treated in 2004 were exposed to coercive measures with the highest percentage among patients with organic psychiatric disorders (ICD-10 F0) (28.0%). Coercive measures were applied a mean 5.4 times per case and lasted a mean 9.7 h each. The incidence and duration of coercive measures varied highly between different diagnostic groups and different hospitals. Use of detailed guidelines for seclusion and restraint was associated with a lower incidence of coercive measures. DISCUSSION: Data interpretation should consider numerous confounding factors such as case mix and hospital characteristics. Suggestions on how to cope with ethical and technical problems in the processing of large multi-site data sets in routine clinical use are made.