Contribution of medico-administrative databases to health vigilance: example of post-oocyte retrieval infections.

STUDY QUESTION: Can we monitor post-oocyte retrieval infections in the French national health data system to complement the French ART vigilance system? SUMMARY ANSWER: Medico-administrative databases provide a more comprehensive view of post-oocyte retrieval infections and can be used to detect abnormal increases in frequency and outlier ART centers as a complementary tool to the ART vigilance system. WHAT IS KNOWN ALREADY: The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has set up a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. STUDY DESIGN, SIZE, DURATION: The study population was identified from the comprehensive French national hospital discharge database. It included women under 46 years of age undergoing an oocyte retrieval in 2019, classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF) , fertility preservation (FP), and oocyte donation (OD) . The study population included 52 098 women who had undergone 65 948 oocyte retrievals in 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Hospital stays and delivery of antibiotics within 31 days after oocyte retrieval were analyzed. Women and infections were characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay, type of antibiotherapy, etc.). Multivariate analysis was performed to determine the relation between the occurrence of infection and women's characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot and a box plot were used to compare the infection rate per center with the national average and to detect outliers. MAIN RESULTS AND THE ROLE OF CHANCE: Infections in the month following the oocyte retrieval represented 6.9% of the procedures in 2019 (n = 4522). Of these infections, 112 were hospitalized (0.2% of oocyte retrievals), and 4410 were non-hospitalized (6.7% of oocyte retrievals). The hospitalized infections were essentially gynecological infections (40.9%) and urinary tract infections (23.5%). In 87.9% of non-hospitalized infections, a single antibiotic therapy was prescribed. Mixed-effect model analysis showed that the risk of infection was significantly higher in women under 30 years of age, in the FP population, in supplementary universal health coverage (CMU-C) beneficiaries, and women with endometriosis. Funnel plot and box plot analysis showed that three ART centers have an infection rate significantly higher than the national average. In the three centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. LIMITATIONS, REASONS FOR CAUTION: Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Another limitation of this study is that we cannot confirm an attributable relation between the infection and the ART procedure, even if the delay of 31 days after oocyte retrieval is consistent with the occurrence of a post-retrieval complication. In addition, antibiotics may be prescribed as a 'precautionary' measure in certain situations (women with a susceptibility to infection, complicated procedures), or as antibiotic prophylaxis for embryo transfer. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limits in identifying post-ART infections in medico-administrative databases, this approach is a promising way to complement the ART vigilance reporting system. This concept developed for infections will also be generalized to other complications with regular feedback to professionals. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought for the study. The study was supported by the Agence de la biomédecine, France. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Overview of hospitalizations in women undergoing oocyte retrieval for ART in the French national health data system.

STUDY QUESTION: What is the incidence rate of complications in women undergoing ART procedures compared to the period prior to their first oocyte retrieval? SUMMARY ANSWER: The study shows a significant increase in the post-ART incidence rate of some complications but a low overall rate of occurrence relative to the total number of oocyte retrievals. WHAT IS KNOWN ALREADY: ART, widely used in Europe, accounts for 3.3% of births in France. The various studies of ART complications are fairly reassuring, showing relatively low overall complication rates but only few studies have used exhaustive national registers. STUDY DESIGN, SIZE, DURATION: The cohort for this study was identified from the comprehensive French national hospital-discharge database and includes women under 50 years with a first oocyte retrieval (T0) in 2012-2017, classified in three population subgroups according to the indication for oocyte retrieval: infertility (IF), oocyte donation (OD), and fertility preservation (FP). This study includes 156 916 women whose first oocyte retrieval occurred in 2012-2017 and 542 775 hospitalizations in 2010-2019 (excluding first retrieval). PARTICIPANTS/MATERIALS, SETTING, METHODS: Hospitalizations for complications or others events (oocyte retrieval, delivery, pregnancy loss, and death in the hospital) during the 2 years before (control period) and after their first oocyte retrieval (post-oocyte retrieval period) were compared and expressed per 10 000 person-months (pm). MAIN RESULTS AND THE ROLE OF CHANCE: In the IF subgroup, incidence rates were significantly higher after (vs before) retrieval for hospitalized ovarian hyperstimulation syndrome (OHSS) (162 vs 6/10 000 pm), adnexal torsion (14 vs 3), venous thrombosis (8 vs 1), arterial thrombosis (3 vs 1), trauma (2 vs 1), and significantly lower for infections (61 vs 87). The higher incidences of OHSS, adnexal torsion and venous thrombosis could only partially be explained by the occurrence of pregnancy.In the FP subgroup, incidence increased significantly after (vs before) retrieval for hospitalized OHSS (55 vs 0), venous thrombosis (59 vs 4), and infections (176 vs 56). For the OD subgroup, hospitalized OHSS (116 vs 0) and bleeding (24 vs 0) were significantly higher after (vs before) retrieval. LIMITATIONS, REASONS FOR CAUTION: The French national health data system, despite all its advantages, present some limitations such as the risk of coding errors. The unavailability of some personal information and the absence of consideration of risk factors prevented us from adjusting the risk. Finally, only complications resulting in hospitalization were analyzed which probably leads to their underestimation. WIDER IMPLICATIONS OF THE FINDINGS: The use of medico-administrative bases will be a valuable tool in public health and will furnish a better overview of the complications. Further studies are needed to complete this analysis. Adding information on drugs would help to better define T0 and less severe complications. STUDY FUNDING/COMPETING INTEREST(S): N/A. TRIAL REGISTRATION NUMBER: N/A.

Long-term outcome of patients undergoing in-vitro fertilisation in France: The outcome study.

The Outcome study examines the fate of 4083 patients beginning IVF in 41 IVF centres, between January 2010 and December 2013. Cumulative live birth rate per patient (CLBR), the best reflection of IVF efficacy, is rarely presented in publications as it requires long-term follow-up, including all successive cycles, and pregnancies outcome. Analysis of international publications shows an average CLBR of 41.6 % and a drop-out rate of 49.5 %, both greatly varying by country and IVF centres. Because of the frequency with which patients change centre (8%), the Outcome study distinguishes patients with a past history of IVF in another centre (CLBR=47.2 %) and patients undergoing their first true cycle (CLBR=56.4 %). Survival techniques by Competing Risk, intended to take account of drop-out and lost to follow-up, assessed the overall CLBR as being 65.4 %. Differences in performance between centres are considerable for both CLBR (32-64%) and Performance Index, taking account of the number of cycles required to achieve a pregnancy (2-5). Multiple variance logistic regression analysis shows that the indicators influencing performance are age, parity, number of oocytes, smoking habit and overweight. These indicators are independent each other and are influencing performance in a high significant way. After adjusting for these indicators, the differences between centres are reduced but remain large and very significant. No centre appears to have specific expertise in the management of patients with adverse indicators. The Outcome study therefore confirms that the large differences in performance between centres are not explained by a difference in the treated population.

Follicular flushing versus direct aspiration in poor responder IVF patients: a randomized prospective study.

OBJECTIVE: To compare follicular flushing with a double-lumen needle with direct aspiration on the number of oocytes collected in a poor responder population in IVF. STUDY DESIGN: We conducted a randomized controlled prospective single-center study between March 2011 and June 2016 at the ART center in the Medico-Surgical and Obstetric Center in Schiltigheim, France. Patients undergoing IVF who had ≤ 4 follicles ≥ 14 mm on the day of HCG administration were recruited and then randomized to one of two groups : simple aspiration group (= NO FLUSH) with a single-lumen 17-gauge needle or follicular flushing group (= FLUSH) which underwent oocyte puncture with aspiration and follicular flushing with a double-lumen 17-gauge needle. The primary end-point was the number of oocytes collected. Secondary assessment criteria were the fertilization rate, the number of transferable embryos, the number of clinical pregnancies and their outcome. RESULTS: 252 patients were included: 127 in the Flush group and 125 in the No flush The number of oocytes retrieved per patient was significantly lower in the FLUSH group: 2.41 than in the NO FLUSH group: 3.42 (p < 0.001). The number of transferable embryos, fertilization rate (68.8 % in the FLUSH group versus 75 % p = 0.682), or pregnancy rate weren't different but (15 versus 13). However the number of failed punctures was significantly higher in the FLUSH group (11 % versus 3.2 % p = 0.016) and the duration of oocyte retrieval was significantly longer in the FLUSH group where the median time was 10 min whereas it was only 7 min in the NO FLUSH group, p < 0.001 CONCLUSION: Follicular flushing in poor responders is not beneficial and could be detrimental with an increasing procedure time and less oocytes retrieved.

Inter-observer agreement in clinical decision-making for abnormal cardiotocogram (CTG) during labour: a comparison between CTG and CTG plus STAN.

OBJECTIVE: To compare inter-observer agreement for clinical decision-making with cardiotocography (CTG) and combined CTG with ST-segment analysis (STAN). DESIGN: Experimental study. SETTING: Three hospital obstetrics departments in France. POPULATION: Thirty randomly selected nonreassuring CTG recordings during labour of women with singleton term pregnancies in cephalic position. METHODS: Seven obstetricians independently assessed the tracings, displayed in a random order on their computers, on two separate sessions, the first without and the second with STAN information. The observers received clinical information about the labour as the tracings continued and were asked whether they would intervene. For analysis, we considered that intervention was justified for the neonates with pH < 7.05 and that nonintervention was justified for those with a pH > 7.10 after spontaneous delivery. MAIN OUTCOME MEASURES: Kappa values and rates of inter-observer agreement for intervention and for nonintervention. RESULTS: Kappa for inter-observer agreement was 0.50 (0.29-0.69) with CTG, and 0.67 (0.48-0.81) with CTG + STAN. The rate of inter-observer agreement for the decision to intervene was 73% (68-77%) with CTG and 70% (66-75%) with CTG + STAN (P = 0.4), and for the nonintervention decision it was 48% (42-54%) and 69% (64-74%), respectively (P < 0.0001). The rate of agreement for justified intervention was 94% (91-97%) with CTG and 85% (80-90%) with CTG + STAN (P < 0.001) and for justified nonintervention, 56% (48-63%) with CTG and 84% (79-89%) with CTG + STAN (P < 0.0001). CONCLUSIONS: In cases with abnormal CTG, ST analysis may improve consistency in clinical decision-making and decrease unnecessary interventions, but may also lead on rare occasions to unjustified decisions not to intervene.

Preservation of fertility in surgery of benign and borderline malignant ovarian tumors.

Benign ovarian tumors occur in 7% of women during their procreative years and involve both organic and functional tumors. The average age of onset for borderline ovarian tumors is ten years younger than that for ovarian cancers. Women with benign and borderline malignant ovarian tumors are therefore more likely to be affected by fertility issues. The causal link between infertility and benign ovarian tumor stems more from the therapeutic strategies adopted than from the histological nature of the benign ovarian tumor. The question of fertility preservation must therefore be addressed in the management of these patients through respect for "correct" surgical indications, through gestures centered around ovarian preservation, and finally, if necessary, by recourse to fertility preservation techniques.

What are the likely IVF/ICSI outcomes if there is a discrepancy between serum AMH and FSH levels? A multicenter retrospective study.

OBJECTIVE: The principal outcome was to assess the ovarian response to controlled hyperstimulation during in vitro fertilization (IVF) with or without micro-injection (ICSI) in patients whom ovarian reserve testing revealed a discrepancy between the serum levels of FSH and AMH. The secondary outcome was to determine whether AMH and FSH profiles could predict the IVF/ICSI response. STUDY DESIGN: This was a multicenter, retrospective study analysing all controlled ovarian hyperstimulation cycles with attempted fresh embryo transfer(s) carried out during IVF/ICSI treatment and in which the AMH level had been assayed between January 01, 2008 and December 31, 2011. This enabled us to form 2 control groups (NOR, normal ovarian reserve: normal AMH and FSH and DOR, diminished ovarian reserve: diminished AMH, increased FSH) and 2 study groups (DAMH: diminished AMH, normal FSH and NAMH: normal AMH, increased FSH). The principal assessment criterion was quantitative ovarian response to stimulation defined by the mean number of oocytes punctured, the secondary assessment criterion the qualitative response to stimulation defined by the pregnancy rate per cycle. RESULTS: We were able to analyse 1803 stimulation cycles. The mean number of oocytes punctured was significantly reduced in the DAMH and DOR groups compared to the NAMH and NOR groups (5.2±3.9 and 4.1±3.3 vs. 11.5±7 and 9.5±5.6, respectively [P<0.01]). The pregnancy rate per initiated cycle was significantly reduced in the DAMH and DOR groups compared to the NAMH and NOR groups (20% and 24% vs. 32 and 35%, respectively [P<0.01]). Live birth rates did not differ between the groups however. Multivariate analysis with logistic regression revealed that AMH, FSH and age independently had an effect on the number of oocytes punctured, although the effect exerted by AMH seemed to be preponderant (OR: 2.75: 95%CI [2.39-3.19]). AMH appeared to be the sole factor independently predictive of pregnancy per cycle. CONCLUSION: The serum AMH level appears to provide an additional item of discriminatory information, which should not be overlooked. Ovarian reserve work-up should include routine AMH assay.

[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.

[Amniotic fluid embolism: two case reports]. / Embolie de liquide amniotique: à propos de deux cas.

We report two cases of amniotic fluid embolism, confirmed by histological examination. Both patients had an immediate post-partum haemorrhage that required an haemostatic hysterectomy. A typical symptomatology of amniotic fluid embolism revelated the first case. The patient survived without any sequelae. In the second case, amniotic fluid embolism occurred immediately after the delivery. The patient developed an acute respiratory distress with a shock syndrome. Despite haemostatic hysterectomy and resuscitative efforts, she died 6 days later.

[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.

[Isolated and recurrent hydrothorax during ovarian stimulation]. / Hydrothorax isolé et récidivant au décours de stimulations ovariennes.

Acute, insulated hydrothorax can be observed after ovulation induction without other signs of hyperstimulation. Usually, it is unilateral, localized on the right side and associated with ongoing pregnancy. We regularly noted a good outcome although the pathogenesis of this affection is still enigmatic. It may recur in the case of a new ovarian stimulation.