Mitochondrial DNA content reduction in the most fertile spermatozoa is accompanied by increased mitochondrial DNA rearrangement.

STUDY QUESTION: Is there an association between male fertility and spermatozoa mitochondrial DNA (mtDNA) copy number and genome rearrangements? SUMMARY ANSWER: Normal spermatozoa not only have a lower mtDNA copy number but also more DNA rearrangements than spermatozoa of men with severe oligoasthenospermia (SOA). WHAT IS KNOWN ALREADY: While there is a consensus that mtDNA content is decreased in the most fertile spermatozoa, the role of mtDNA sequence alteration in male infertility is unclear. High-throughput sequencing, which allows an exhaustive analysis of mtDNA rearrangements and mutations, could be helpful in this context, but has yet to be used. STUDY DESIGN, SIZE, DURATION: This is an observational study of semen samples obtained from 44 men undergoing ART at an academic infertility centre in France, from October 2018 to November 2020. The men were classified into two groups: 20 men in the SOA group and 24 men with normal semen parameters in the control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: For each patient and control, mtDNA was isolated from sperm fractions from the 40% and 90% layers of the density gradient. The average mtDNA content of each sample was assessed using digital PCR. Deep sequencing was performed using next-generation sequencing. Signal processing and base calling were performed via the embedded pre-processing pipeline, the variants were analysed using an in-house workflow and a dedicated tool, based on soft-clipping, was used to study large mtDNA rearrangements. The distribution and the type of rearrangements and variants were compared between patients with SOA and controls on one hand, and between the 40% and 90% gradient layers, on the other hand. MAIN RESULTS AND THE ROLE OF CHANCE: The mtDNA content of spermatozoa in the SOA group was significantly higher than in the control group (P < 0.0001). Moreover, mtDNA content was significantly higher in spermatozoa from the 40% layer (the most fertile spermatozoa) compared to the 90% layer, both in the SOA (P = 0.02) and the control group (P < 0.0001). The frequency of large mtDNA deletions and duplications was significantly higher in the control group (P = 0.002). Most of these rearrangements are potentially related to DNA breaks and their number was reduced by the removal of the linear mtDNA from the samples. Heteroplasmic variants were found more frequently in the SOA group (P = 0.05) and in the 40% layer (P = 0.03), but none had any obvious functional consequence. LIMITATIONS, REASONS FOR CAUTION: Our findings are novel and significant but should be verified in larger cohorts and other types of male infertility. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that sperm mtDNA rearrangements are not necessarily associated with mitochondrial dysfunction and male infertility. Instead, they seem to be concomitant with the process of mtDNA content reduction in the most potentially fertile spermatozoa. Furthermore, they refute the hypothesis that, in the case of mtDNA alteration, a compensatory mechanism allows an increase in mtDNA copy number to rectify the energy deficit. The increased frequency of mtDNA rearrangements in the most fertile spermatozoa is a novel result that offers new insight into the relation between sperm quality and mtDNA. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Angers University Hospital (grant AOI CHU Angers 2018), Angers University and the French national research centres INSERM and CNRS. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Assessment of operator performance during oocyte retrievals: residents' learning curve and continuous monitoring of senior physicians.

BACKGROUND: The learning curve cumulative summation test (LC CUSUM test) allows to define an individualized learning curve and determine the moment when clinical proficiency is attained. After acquisition of the skills, the cumulative summation test (CUSUM test) allows to monitor the maintenance of the required level over time. The LC CUSUM test has been frequently used in the field of Obstetrics and Gynecology (Ob/Gyn) for several procedures, but only once for OR. METHODS: We performed a retrospective study at Angers university hospital between May 2017 and September 2018. Seven Ob/Gyn residents and 5 senior physicians were included, and all OR performed during that time (n = 690) were analyzed. The performance index assessed was the oocyte retrieval rate (ORR), defined as the ratio of oocytes retrieved to follicles aspirated. We used the LC CUSUM test to analyze the learning curves of residents, and the CUSUM test to monitor the performance of senior physicians. An ORR ≥50% in 60% of retrievals was defined as the threshold for clinical proficiency. RESULTS: Six hundred seventy-four oocyte retrieval (OR) were included: 315 were performed by residents, 220 by senior physicians, and 139 by both residents and physicians (mixed retrievals). Four residents (57%) reached the threshold after aspirating 82, 67, 53 and 46 ovaries, respectively. The mean number of ovaries aspirated in order to reach clinical proficiency was 62, and the mean number of weeks needed was 21. The duration of the learning period varied between 26 and 80 days. Two senior physicians (40%) remained proficient across the duration of the study, while two physicians (40%) had one statistically "suboptimal" OR, and one physician (20%) had two suboptimal retrievals. CONCLUSION: There is a large variability in the duration of the learning period and the number of procedures needed for a resident to master OR. Senior physicians maintain an adequate performance.

The mitochondrial DNA content of cumulus cells may help predict embryo implantation.

PURPOSE: The quantification of mtDNA in cumulus granulosa cells (CGCs) surrounding an oocyte has been positively linked with morphological embryonic quality. In the present study, we evaluated the link between the amount of mtDNA in CGCs surrounding an oocyte and the chances for the corresponding embryo of implanting and leading to an ongoing pregnancy. METHODS: This is an observational study, performed on 84 oocyte-cumulus-complexes (OCCs) having led to the replacement of an embryo in the maternal uterus, retrieved from 71 patients undergoing IVF with intracytoplasmic sperm. The OCCs were classified in two groups, one including 26 OCCs having led to an implanted embryo and the other including 58 OCCs having led to a non-implanted embryo. The average mtDNA content of CGCs was assessed by using a quantitative real-time PCR technique. RESULTS: Significantly higher mtDNA copy numbers in CGCs were associated with implanted embryos than with non-implanted embryos (mean 215 [sd 375] and 59 [sd 72], respectively; p < 104). Multivariate analysis, taking into account the women's age, the embryo quality, and the AMH level, suggests an independent relationship between the mtDNA content of CGCs and the potential of embryo implantation. CONCLUSION: During in vitro fertilization (IVF) procedures, the probability of the implantation of the embryo appears to be closely correlated to the mtDNA copy numbers in the CGCs. Our results highlight the interest of mtDNA quantification in GCGs as a biomarker of the potential of embryo implantation.

The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality.

STUDY QUESTION: Could the mitochondrial DNA (mtDNA) content of cumulus granulosa cells (CGCs) be related to oocyte competence? SUMMARY ANSWER: The quality of embryos obtained during IVF procedures appears to be linked to mtDNA copy numbers in the CGCs. WHAT IS KNOWN ALREADY: Oocyte quality is linked to oocyte mtDNA content in the human and other species, and the mtDNA copy number of the oocyte is related to that of the corresponding CGCs. Moreover, the quantification of CGC mtDNA has recently been proposed as a biomarker of embryo viability. STUDY DESIGN SIZE, DURATION: An observational study was performed on 452 oocyte-cumulus complexes retrieved from 62 patients undergoing ICSI at the ART Center of the University Hospital of Angers, France, from January to May 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: The average mtDNA content of CGCs was assessed by using a quantitative real-time PCR technique. The relationship between CGC mtDNA content and oocyte maturity and fertilizability, on one hand, and embryo quality, on the other, was investigated using univariate and multivariate generalized models with fixed and mixed effects. MAIN RESULTS AND THE ROLE OF CHANCE: No relationship was found between CGC mtDNA content and oocyte maturity or fertilizability. In contrast, there was a significant link between the content of mtDNA in CGCs surrounding an oocyte and the embryo quality, with significantly higher mtDNA copy numbers being associated with good quality embryos compared with fair or poor quality embryos [interquartile range, respectively, 738 (250-1228) and 342 (159-818); P = 0.006]. However, the indication provided by the quantification of CGC mtDNA concerning the eventuality of good embryo quality was seriously subject to patient effect (AUC = 0.806, 95%CI = 0.719-0.869). The quantity of CGC mtDNA was influenced by BMI and smoking. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The quantification of CGC mtDNA may indicate embryo quality. However, since it is affected by patient specificity, it should be used with caution. It remains to be seen whether this marker could directly predict the implantation capacity of the embryo, which is the main objective in IVF practice. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that the quantification of CGC mtDNA may be a novel biomarker of embryo viability. However, patient specificity makes it impossible to establish a general threshold value, valid for all patients. Nevertheless, further studies are needed to determine whether the quantification of CGC mtDNA may, in combination with the morpho-kinetic method, offer an additional criterion for selecting the best embryo for transfer from a given cohort. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University Hospital of Angers, the University of Angers, France, and the French national research centres INSERM and the CNRS. There were no competing interests.

Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing.

STUDY QUESTION: Does ovarian ageing increase the number of heteroplasmic mitochondrial DNA (mtDNA) point mutations in oocytes? SUMMARY ANSWER: Our results suggest that oocytes are not subject to the accumulation of mtDNA point mutations during ovarian ageing. WHAT IS KNOWN ALREADY: Ageing is associated with the alteration of mtDNA integrity in various tissues. Primary oocytes, present in the ovary since embryonic life, may accumulate mtDNA mutations during the process of ovarian ageing. STUDY DESIGN, SIZE, DURATION: This was an observational study of 53 immature oocyte-cumulus complexes retrieved from 35 women undergoing IVF at the University Hospital of Angers, France, from March 2013 to March 2014. The women were classified in two groups, one including 19 women showing signs of ovarian ageing objectified by a diminished ovarian reserve (DOR), and the other, including 16 women with a normal ovarian reserve (NOR), which served as a control group. PARTICIPANTS/MATERIALS, SETTING, METHODS: mtDNA was extracted from isolated oocytes, and from their corresponding cumulus cells (CCs) considered as a somatic cell compartment. The average mtDNA content of each sample was assessed by using a quantitative real-time PCR technique. Deep sequencing was performed using the Ion Torrent Proton for Next-Generation Sequencing. Signal processing and base calling were done by the embedded pre-processing pipeline and the variants were analyzed using an in-house workflow. The distribution of the different variants between DOR and NOR patients, on one hand, and oocyte and CCs, on the other, was analyzed with the generalized mixed linear model to take into account the cluster of cells belonging to a given mother. MAIN RESULTS AND THE ROLE OF CHANCE: There were no significant differences between the numbers of mtDNA variants between the DOR and the NOR patients, either in the oocytes (P = 0.867) or in the surrounding CCs (P = 0.154). There were also no differences in terms of variants with potential functional consequences. De-novo mtDNA variants were found in 28% of the oocytes and in 66% of the CCs with the mean number of variants being significantly different (respectively 0.321, SD = 0.547 and 1.075, SD = 1.158) (P < 0.0001). Variants with a potential functional consequence were also overrepresented in CCs compared with oocytes (P = 0.0019). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Limitations may be due to the use of immature oocytes discarded during the assisted reproductive technology procedure, the small size of the sample, and the high-throughput sequencing technology that might not have detected heteroplasmy levels lower than 2%. WIDER IMPLICATIONS OF THE FINDINGS: The alteration of mtDNA integrity in oocytes during ovarian ageing is a recurring question to which our pilot study suggests a reassuring answer. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University Hospital of Angers, the University of Angers, France, and the French national research centers, INSERM and the CNRS. There are nocompeting interests.

Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve.

STUDY QUESTION: Does the metabolomic profile of the follicular fluid (FF) of patients with a diminished ovarian reserve (DOR) differ from that of patients with a normal ovarian reserve (NOR)? SUMMARY ANSWER: The metabolomic signature of the FF reveals a significant decrease in polyunsaturated choline plasmalogens and methyl arginine transferase activity in DOR patients compared to NOR patients. WHAT IS KNOWN ALREADY: The composition of the FF reflects the exchanges between the oocyte and its microenvironment during its acquisition of gametic competence. Studies of the FF have allowed identification of biomarkers and metabolic pathways involved in various pathologies affecting oocyte quality, but no large metabolomic analysis in the context of ovarian ageing and DOR has been undertaken so far. STUDY DESIGN, SIZE, DURATION: This was an observational study of the FF retrieved from 57 women undergoing in vitro fertilization at the University Hospital of Angers, France, from November 2015 to September 2016. The women were classified in two groups: one including 28 DOR patients, and the other including 29 NOR patients, serving as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were enrolled in the morning of oocyte retrieval after ovarian stimulation. Once the oocytes were isolated for fertilization and culture, the FF was pooled and centrifuged for analysis. A targeted quantitative metabolomic analysis was performed using high-performance liquid chromatography coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. The FF levels of 188 metabolites and several sums and ratios of metabolic significance were assessed by multivariate and univariate analyses. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 136 metabolites were accurately quantified and used for calculating 23 sums and ratios. Samples were randomly divided into training and validation sets. The training set, allowed the construction of multivariate statistical models with a projection-supervised method, i.e. orthogonal partial least squares discriminant analysis (OPLS-DA), applied to the full set of metabolites, or the penalized least absolute shrinkage and selection operator with logistic regression (LASSO-LR), applied to the ratios and sums of the metabolites. Both multivariate models showed good predictive performances when applied to the validation set. The final penalized model retained the three most significant variables, i.e. the total dimethylarginine-to-arginine ratio (Total DMA/Arginine), the sum of the polyunsaturated choline plasmalogens (PUFA ae), and the patient's age. The negative coefficients of Total DMA/Arginine and PUFA ae indicated that these FF variables had lower values in DOR patients than in NOR patients. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This study presents two limitations. First, with this targeted metabolomics analysis, we have explored only a limited portion of the FF metabolome. Second, although the signature found was highly significant, the mechanism underlying the dysfunction remains undetermined. WIDER IMPLICATIONS OF THE FINDINGS: The understanding of the mechanisms implied in ovarian ageing is essential for providing an adequate response to affected women desiring pregnancy. Our study proposes an incoming signature that may open new paths towards this goal. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the University Hospital of Angers, the University of Angers, and the French national research centers, INSERM and the CNRS. There were no competing interests.

Planned caesarean in the interventional radiology cath lab to enable immediate uterine artery embolization for the conservative treatment of placenta accreta.

AIM: To evaluate the feasibility and efficacy of routine uterine artery embolization (UAE) immediately after planned caesareans performed in the cath lab for conservative treatment of placenta accreta. MATERIALS AND METHODS: A retrospective study included all patients who had a planned caesarean in the cath lab for conservative treatment of placenta accreta at Angers University Hospital, which is a tertiary care centre, from April 2001 to September 2010. Twelve patients underwent UAE immediately after caesarean with the placenta left partially or totally in situ. The success rate of embolization, blood loss, and complications were reported. RESULTS: Diagnosis of abnormal placentation was confirmed by caesarean findings in 14 cases. Four patients had a percreta form with bladder invasion. In seven cases blood loss was insignificant and UAE was prophylactic; no secondary haemorrhage was observed in this group. Postpartum haemorrhage occurred in five cases: control of immediate postpartum bleeding by embolization was successful in three and failed in two leading to hysterectomy. In one case uterine necrosis occurred 6 weeks after embolization, requiring a hysterectomy. Delayed complications resulted in hysterectomy and partial bladder resection 3 months after delivery for one of the patients with placenta percreta. CONCLUSION: UAE immediately after a caesarean performed in the cath lab is a feasible therapeutic option for conservative treatment of placenta accreta. Advantages include reducing stress and risks associated with transferring women with potentially unstable haemodynamics.

Impact of endometrial preparation on early pregnancy loss and live birth rate after frozen embryo transfer: a large multicenter cohort study (14 421 frozen cycles).

STUDY QUESTION: Does the endometrial preparation protocol (artificial cycle (AC) vs natural cycle (NC) vs stimulated cycle (SC)) impact the risk of early pregnancy loss and live birth rate after frozen/thawed embryo transfer (FET)? SUMMARY ANSWER: In FET, ACs were significantly associated with a higher pregnancy loss rate and a lower live birth rate compared with SC or NC. WHAT IS KNOWN ALREADY: To date, there is no consensus on the optimal endometrial preparation in terms of outcomes. Although some studies have reported a higher pregnancy loss rate using AC compared with NC or SC, no significant difference was found concerning the pregnancy rate or live birth rate. Furthermore, no study has compared the three protocols in a large population. STUDY DESIGN SIZE DURATION: A multicenter retrospective cohort study was conducted in nine reproductive health units in France using the same software to record medical files between 1 January 2012 and 31 December 2016. FET using endometrial preparation by AC, modified NC or SC were included. The primary outcome was the pregnancy loss rate at 10 weeks of gestation. The sample size required was calculated to detect an increase of 5% in the pregnancy loss rate (21-26%), with an alpha risk of 0.5 and a power of 0.8. We calculated that 1126 pregnancies were needed in each group, i.e. 3378 in total. PARTICIPANTS/MATERIALS SETTING METHODS: Data were collected by automatic extraction using the same protocol. All consecutive autologous FET cycles were included: 14 421 cycles (AC: n = 8139; NC: n = 3126; SC: n = 3156) corresponding to 3844 pregnancies (hCG > 100 IU/l) (AC: n = 2214; NC: n = 812; SC: n = 818). Each center completed an online questionnaire describing its routine practice for FET, particularly the reason for choosing one protocol over another. MAIN RESULTS AND THE ROLE OF CHANCE: AC represented 56.5% of FET cycles. Mean age of women was 33.5 (SD ± 4.3) years. The mean number of embryos transferred was 1.5 (±0.5). Groups were comparable, except for history of ovulation disorders (P = 0.01) and prior delivery (P = 0.03), which were significantly higher with AC. Overall, the early pregnancy loss rate was 31.5% (AC: 36.5%; NC: 25.6%; SC: 23.6%). Univariable analysis showed a significant association between early pregnancy loss rate and age >38 years, history of early pregnancy loss, ovulation disorders and duration of cryopreservation >6 months. After adjustment (multivariable regression), the early pregnancy loss rate remained significantly higher in AC vs NC (odds ratio (OR) 1.63 (95% CI) [1.35-1.97]; P < 0.0001) and in AC vs SC (OR 1.87 [1.55-2.26]; P < 0.0001). The biochemical pregnancy rate (hCG > 10 and lower than 100 IU/l) was comparable between the three protocols: 10.7% per transfer. LIMITATIONS REASONS FOR CAUTION: This study is limited by its retrospective design that generates missing data. Routine practice within centers was heterogeneous. However, luteal phase support and timing of embryo transfer were similar in AC. Univariable analysis showed no difference between centers. Moreover, a large number of parameters were included in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: Our study shows a significant increase in early pregnancy loss when using AC for endometrial preparation before FET. These results suggest either a larger use of NC or SC, or an improvement of AC by individualizing hormone replacement therapy for patients in order to avoid an excess of pregnancy losses. STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflicts of interest in relation to this work. G.P.-B. declares consulting fees from Ferring, Gedeon-Richter, Merck KGaA, Theramex, Teva; Speaker's fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter, Theramex, Teva. N.C. declares consulting fees from Ferring, Merck KGaA, Theramex, Teva; Speaker's fees or equivalent from Merck KGaA, Ferring. C.R. declares a research grant from Ferring, Gedeon-Richter; consulting fees from Gedeon-Richter, Merck KGaA; Speaker's fees or equivalent from Merck KGaA, Ferring, Gedeon-Richter; E.M.d'A. declares Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Theramex, Teva. I.C-D. declares Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, IBSA. N.M. declares a research grant from Merck KGaA, MSD, IBSA; consulting fees from MSD, Ferring, Gedeon-Richter, Merck KGaA; Speaker's fees or equivalent from Merck KGaA, MSD, Ferring, Gedeon-Richter, Teva, Goodlife, General Electrics. TRIAL REGISTRATION NUMBER: N/A.

Comparison of neonatal outcomes of cesarean sections performed under primary or secondary general anesthesia: a retrospective study.

BACKGROUND: The conversion of neuraxial anesthesia (NA) to general anesthesia (GA) during a cesarean section (CS) may be associated with a higher risk of neonatal morbidity by adding the undesirable effects of both these anesthesia techniques. We aimed to compare the neonatal morbidity of non-elective CS performed after conversion from NA to GA (secondary GA) vs. that after GA from the outset (primary GA). METHODS: We performed a monocentric retrospective study at the Angers University Hospital (France). All non-elective CSs performed under GA between January 2015 and December 2019 were included. The CSs were classified using a three-color coding system (green for non-urgent delivery, orange for urgent CS, and red for very urgent CS). The primary neonatal outcome was a composite of umbilical artery pH <7.10 or 5-min Apgar score <7. The crude and adjusted odds ratios (OR) for the risk of neonatal morbidity associated with secondary GA were estimated. RESULTS: We included 247 patients, of whom 101 (41.3%) had a secondary GA and 146 (58.7%) had primary GA. In the secondary GA group, 86.1% (87/101) had epidural anesthesia and 13.9% (14/101) had spinal anesthesia. Multivariate analysis showed no difference in neonatal morbidity between the two groups (adjusted odds ratio 1.18, 95% CI 0.56 to 2.51). CONCLUSIONS: Our study found insufficient evidence to identify a difference in neonatal outcomes between secondary compared with primary GA for CS, regardless of the level of emergency. However, our study is underpowered and additional studies are needed to confirm these data.

[Guidelines for Clinical Practice of the French College of Obstetricians and Gynecologists 2021: Prophylactic procedures associated with gynecologic surgery]. / Recommandations pour Pratique Clinique du Collège des Gynécologues Obstétriciens français 2021 : gestes prophylactiques associés en chirurgie gynécologique.

OBJECTIVE: To draw up recommendations on the use of prophylactic gynecologic procedures during surgery for other indications. DESIGN: A consensus panel of 19 experts was convened. A formal conflict of interest policy was established at the onset of the process and applied throughout. The entire study was performed independently without funding from pharmaceutical companies or medical device manufacturers. The panel applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate the quality of evidence on which the recommendations were based. The authors were advised against making strong recommendations in the presence of low-quality evidence. Some recommendations were ungraded. METHODS: The panel studied 22 key questions on seven prophylactic procedures: 1) salpingectomy, 2) fimbriectomy, 3) salpingo-oophorectomy, 4) ablation of peritoneal endometriosis, 5) adhesiolysis, 6) endometrial excision or ablation, and 7) cervical ablation. RESULTS: The literature search and application of the GRADE system resulted in 34 recommendations. Six were supported by high-quality evidence (GRADE 1+/-) and 28 by low-quality evidence (GRADE 2+/-). Recommendations on two questions were left ungraded due to a lack of evidence in the literature. CONCLUSIONS: A high level of consensus was achieved among the experts regarding the use of prophylactic gynecologic procedures. The ensuing recommendations should result in improved current practice.

Positive impact of simulation training of residents on the patients' psychological experience following pregnancy loss.

OBJECTIVE: Our study aimed to assess the impact of a simulation training program for residents for the disclosure of diagnosis on the psychological experience of couples following a first trimester pregnancy loss (PL). METHODS: We performed an uncontrolled prospective single center, before-after study, at the gynecological emergency department of Angers University Hospital in France, between May 2014 and April 2015. We included all patients who had a confirmed diagnosis of first trimester PL. A self-administering questionnaire (SAQ) that included the short version of the perinatal grief scale (PGS) and questions about the couples' personal experience was sent by mail 8 weeks after the diagnosis. Patients were included before and after simulation training of the residents on the communication of the diagnosis of PL, and scores were compared between the two groups (before and after training). RESULTS: Overall 72 patients fulfilled the inclusion criteria and responded to the SAQ, 45 before and 27 after simulation training. Overall, simulation training significantly lowered the overall PGS (39.4±4.9 vs 57.3±5.6, p=0.03), significantly improved the attitude of the resident when announcing the diagnosis (more considerate (74.1 % vs 48.9 %, p=0.04) and available (59.3 % vs 28.9 %, p=0.01)), and significantly improved the quality of the information given (less incomprehensible (22.2 % vs 46.7 %, p=0.04). Finally, significantly fewer patients reported needing an additional consultation for further information following training (33.3 % vs 73.3 %, p=0.01). CONCLUSION: Simulation training of residents for the disclosure of early pregnancy loss significantly improves the couples' personal experience and decreases the psychological morbidity associated with the communication.

Effect of the use of a video tutorial in addition to simulation in learning the maneuvers for shoulder dystocia.

The development of video tutorials is flourishing and may make it possible to maintain knowledge learned during instruction with simulation. The aim of this study was to assess the effect of adding a video tutorial to a lecture and simulation for learning the maneuvers and protocol for the management of shoulder dystocia. Student midwives and medical students attended a lecture class including instruction about maneuvers and a presentation of an algorithm for the management of shoulder dystocia. They were randomized into two groups. The video group was reminded every two weeks to watch a short tutorial. The control group was reminded to consult the slide show. At the end of two months, they were evaluated by graders. The practice, theory, and global scores of the students in the video group were significantly higher than those of the students in the control group (14.8 vs. 10.4; 5.6 vs. 3.4; and 9.3 vs. 7.0, P<0.001). The scores for the video group improved at the second simulation session, compared with the first (14.8 vs. 9.9; 5.6 vs. 2.9; and 9.3 vs. 7, P<0.001). The addition of a video tutorial improved learning compared to a standard lecture and simulation session alone.

The impact of manual rotation of the occiput posterior position on spontaneous vaginal delivery rate: study protocol for a randomized clinical trial (RMOS).

BACKGROUND: The frequency of posterior presentations (occiput of the fetus towards the sacrum of the mother) in labor is approximately 20% and, of this, 5% remain posterior until the end of labor. These posterior presentations are associated with higher rates of cesarean section and instrumental delivery. Manual rotation of a posterior position in order to rotate the fetus to an anterior position has been proposed in order to reduce the rate of instrumental fetal delivery. No randomized study has compared the efficacy of this procedure to expectant management. We therefore propose a monocentric, interventional, randomized, prospective study to show the superiority of vaginal delivery rates using the manual rotation of the posterior position at full dilation over expectant management. METHODS: Ultrasound imaging of the presentation will be performed at full dilation on all the singleton pregnancies for which a clinical suspicion of a posterior position was raised at more than 37 weeks' gestation (WG). In the event of an ultrasound confirming a posterior position, the patient will be randomized into an experimental group (manual rotation) or a control group (expectative management with no rotation). For a power of 90% and the hypothesis that vaginal deliveries will increase by 20%, (10% of patients lost to follow-up) 238 patients will need to be included in the study. The primary endpoint will be the rate of spontaneous vaginal deliveries (expected rate without rotation: 60%). The secondary endpoints will be the rate of fetal extractions (cesarean or instrumental) and the maternal and fetal morbidity and mortality rates. The intent-to-treat study will be conducted over 24 months. Recruitment started in February 2017. To achieve the primary objective, we will perform a test comparing the number of spontaneous vaginal deliveries in the two groups using Pearson's chi-squared test (provided that the conditions for using this test are satisfactory in terms of numbers). In the event that this test cannot be performed, we will use Fisher's exact test. DISCUSSION: Given that the efficacy of manual rotation has not been proven with a high level of evidence, the practice of this technique is not systematically recommended by scholarly societies and is, therefore, rarely performed by obstetric gynecologists. If our hypothesis regarding the superiority of manual rotation is confirmed, our study will help change delivery practices in cases of posterior fetal position. An increase in the rates of vaginal delivery will help decrease the short- and long-term rates of morbidity and mortality following cesarean section. Manual rotation is a simple and effective method with a success rate of almost 90%. Several preliminary studies have shown that manual rotation is associated with reduced rates for fetal extraction and maternal complications: Shaffer has shown that the cesarean section rate is lower in patients for whom a manual rotation is performed successfully (2%) with a 9% rate of cesarean sections when manual rotation is performed versus 41% when it is not performed. Le Ray has shown that manual rotation significantly reduces vaginal delivery rates via fetal extraction (23.2% vs 38.7%, p < 0.01). However, manual rotation is not systematically performed due to the absence of proof of its efficacy in retrospective studies and quasi-experimental before/after studies. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03009435 . Registered on 30 December 2016.

Can the risks associated with uterine sarcoma morcellation really be prevented? Overview of the role of uterine morcellation in 2018.

OBJECTIVES: The objective of this literature review is to reiterate the epidemiology, clinical signs, and radiological signs that should be consistent with a uterine sarcoma as well as the precautionary pre- and postoperative principles that help prevent morcellation of uterine sarcomas when treating patients with uterine fibroids. METHOD: We conducted this literature review by consulting the Pubmed, Medline, and Cochrane Systematic Review databases up to 28/02/2017 using the following keywords: fibroid, myoma, leiomyoma, sarcoma, leiosarcoma, uterine cancer, myomectomy, hysterectomy, morcellation, and uterine morcellation. We also used the reference lists of the selected articles to find more data on the websites of North-American and European learned societies that specialise in obstetrics and gynaecology. RESULTS: In the case of morcellation of uterine fibroids, the risk of an undiagnosed uterine sarcoma is estimated to be between 1 in 278 to 1 in 1960 women. Preoperative examination, free informed consent following discussion about the risks and complications associated with morcellation, as well as research on the contraindications to the use of morcellation are the crucial points addressed by learned societies. The main solution recommended at present is morcellation confined to a laparoscopic bag. CONCLUSION: There is a risk of morcellating an occult sarcoma when performing a myomectomyor hysterectomy for fibroids. Implementing the use of morcellation containment bags should be the norm. The use of minimally invasive surgery (laparoscopic orvaginal) and the associated benefit-risk ratio compared to a laparotomy should also be discussed with the patient before the operation.

Surgery using plasma energy for deep endometriosis: A quality of life assessment.

OBJECTIVE: The principal objective of our study was to assess women's quality of life (QoL) after surgery for Deep Endometriosis (DE), according to the surgical technique used. MATERIAL AND METHODS: Qualitative single-center survey in the department of obstetrics and gynecology, Angers University Hospital Center, France. All women who underwent surgery for DE from January 2011 to December 2015 were contacted by phone. The Endometriosis Health Profile-5 score was used to assess QoL before and after the surgery. Fifty-two women (response rate=86%) were included and classified into 3 groups according to the surgical technique used: simple shaving, shaving exclusively or in part by plasma vaporization (plasma), and resection. RESULTS: The 3 groups were comparable for surgical history, preoperative QoL score, and characteristics of endometriotic lesions (size and site). All DE symptoms and QoL scores improved significantly after the surgery, all techniques combined (P<0.01). QoL scores for women who had plasma shaving or complete resection were significantly higher than those for women with simple shaving (respectively, 375 [225-800] and 450 [-50 to 725] vs 275 [-100 to 600]; P=0.04). Self-image significantly improved only in the plasma group (P=0.03). The complete resection group had longer hospitals stays than the other groups (P=0.001), as well as a higher surgical revision rate (23% vs 0%; P=0.02). CONCLUSION: Plasma and complete resection improved QoL similarly for women with DE, both more than shaving alone. The advantage of plasma vaporization lies in the lesser morbidity and better self-image, both better than in women with resection.

[New medical treatments for painful endometriosis: CNGOF-HAS Endometriosis Guidelines]. / Place des nouveaux traitements médicaux dans l'endométriose douloureuse, RPC Endométriose CNGOF-HAS.

OBJECTIVE: The objective of this work is to evaluate the place of new treatments in the management of endometriosis outside the context of infertility. METHODS: A review of the literature was conducted by consulting Medline data until July 2017. RESULTS: Dienogest is effective compared to placebo in short term (NP2) and long term (NP4) for the treatment of painful endometriosis. In comparison with GnRH agonists, dienogest is also effective in terms of decreased pain and improved quality of life in non-operated patients (NP2) as well as for recurrence of lesions and symptomatology postoperatively (NP2). Data on GnRH antagonists, selective progesterone receptor modulators as well as selective inhibitors (anti-TNF-α, matrix metalloprotease inhibitors, angiogenesis growth factor inhibitors) are insufficient to provide evidence of interest in clinical practice for the management of painful endometriosis (NP3). CONCLUSION: Dienogest is recommended as second-line therapy for the management of painful endometriosis (Grade B). Because of lack of evidence, aromatase inhibitors, elagolix, SERM, SPRM and anti-TNF-α are not recommended for the management of painful endometriosis (Grade C).

Surgical treatment of septate uterus in cases of primary infertility and before assisted reproductive technologies.

Septate uterus is the most common congenital uterine malformation in women with infertility. Several criteria are available for the definition of septate uteri, such as the one proposed by the European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynecological Endoscopy (ESGE) (ESHRE/ESGE), or by the American Society for Reproductive Medicine (ASRM), with notable differences between the two. Recently, a simplified classification was proposed by the Congenital Uterine Malformations Experts (CUME), where a septum is defined as an internal indentation depth≥10mm. To date, there is no consensus on the management of women with a septate uterus and infertility. We have performed an extensive literature appraisal and reviewed all the available international guidelines in order to propose a management strategy for infertile patients with a uterine septum. Hysteroscopic septum incision seems to improve natural conception rates in the year following surgery. Moreover, it improves in vitro fertilization (IVF) outcomes when performed before the embryo transfer, by improving embryo implantation rates. On the other hand, for patients with an arcuate uterus (indentation<1.5cm according to the ASRM guidelines) and infertility, it seems that assisted reproductive technologies are the most appropriate first line treatment. However, in cases of recurrent implantation failure or recurrent pregnancy loss following IVF, hysteroscopic section could be proposed. Overall, we recommend hysteroscopic septum incision for patients with primary infertility, and for patients undergoing assisted reproductive technologies.

[In vitro fertilization versus conversion to intrauterine insemination in patients with poor response to controlled ovarian hyperstimulation]. / Réponse insuffisante à la stimulation en vue de FIV : maintenir la ponction ou choisir l' insémination ?

In women undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF), a poor ovarian response, defined as three of fewer mature follicles, can lead to cancellation of the cycle. However, in women with at least one patent tube and normal semen parameters, conversion to intrauterine insemination (IUI) is considered an option, offering reasonable pregnancy rates at a lower cost and without the complications associated with oocyte retrieval. Studies have shown that in cycles with only one mature follicle, IVF should be canceled. However, in cycles with 2 or 3 mature follicles, patients have the choice between IVF and conversion to IUI. Some studies have shown that IVF is superior to IUI in such cases, whereas other reports failed to find any difference. Most of these studies are retrospective and limited by the presence of several biases and low numbers of cycles, and to this date, there is no consensus on the best approach. We have thus designed a multicenter, randomized non-inferiority study, comparing live birth rates following conversion to IUI or IVF in patients with 2 or 3 mature follicles in COH cycles. Nine hundred and forty patients will be randomized on trigger day to either IVF or conversion to IUI. Our study will also include a medico-economic analysis.