Comparison of two cancellation strategies to lower the risk of multiple pregnancies in gonadotropin stimulated intrauterine insemination cycles.

OBJECTIVE: To compare two cancellation policies in controlled ovarian stimulation-intrauterine insemination (COS-IUI) cycles to lower the risk of multiple pregnancies (MP). DESIGN: We performed a bicentric retrospective cohort study in two academic medical centers: Angers (group A) and Besançon (group B) University Hospitals. We included 7056 COS-IUI cycles between 2011 and 2019. In group A, cancellation strategy was based on an algorithm taking into account the woman's age, the serum estradiol level, and the number of follicles of 14 mm or greater on ovulation trigger day. In group B, cancellation strategy was case-by-case and physician-dependent, based on the woman's age, number of follicles of 15 mm or greater, and the previous number of failed COS-IUI cycles, without any predefined cut-off. Our main outcome measures were the MP rate (MPR) and the live-birth rate (LBR). RESULTS: We included 884 clinical pregnancies (790 singletons, 86 twins, and 8 triplets) obtained from 6582 COS-IUI cycles. MPR was significantly lower in group A compared with group B (8.1% vs 13.3%, P = 0.01), but LBR were comparable (10.8% vs 11.8%, P = 0.19). Multivariate logistic regression found the following to be risk factors for MP: the "cancellation strategy" effect (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.02-2.60) and the number of follicles of 14 mm or greater (aOR 1.39, 95% CI 1.16-1.66). Cycle cancellation rate for excessive response was significantly lower in group A compared with group B (1.3% vs 2.4%, P < 0.001). CONCLUSIONS: The use of an algorithm based on the woman's age, serum estradiol level and number of follicles of at least 14 mm on trigger day allows the MPR to be reduced without impacting the LBR.

[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.

The correlation between prenatal ultrasound and MRI in isolated periventricular pseudocysts: Analysis of 10 years' experience at the University Hospital of Angers.

BACKGROUND: Periventricular cysts are one of the most extensively documented antenatal brain lesions found through fetal ultrasound at the University Hospital of Angers. The main purpose of our study was to determine the contribution of fetal magnetic resonance imaging (MRI) and postnatal transfontanellar ultrasound (TFU) in the assessment of isolated periventricular cysts found on antenatal ultrasound at the University Hospital of Angers. METHODS: This retrospective, descriptive study was carried out over a 10-year period. Overall, 82 cases were included, divided into two groups according to the type of cysts found on the ultrasound: 13 cases of subependymal pseudocysts (SEPC) and 69 cases of frontal horn cysts (FHC). In all, 43 children underwent a postnatal TFU: seven in the SEPC group and 36 in the FHC group. RESULTS: Our study found excellent agreement between antenatal ultrasound and fetal MRI in the FHC group concerning classification of the cysts (approval rate [TA]: 98.60%; kappa coefficient [κ]: 0.85), their location (TA: 98.80%; κ: 0.91), their number (TA: 78.20%; κ: 0.73), and the detection of FHC (TA: 81.10%; κ: 0.74), as well as a good agreement concerning the detection of SEPC and temporal horn cysts (THC; TA: 99.40% and 95.60%, respectively). Fetal MRI proved to be better in the SEPC group for cyst classification (TA: 66.70%; κ: 0.33), their location (TA: 60%; κ: 0.41), and their number (TA: 53, 30%; κ: 0.45) and the detection of SEPC (TA: 23.10%; κ: 0.14). In both groups, postnatal TFU did not provide additional information compared to MRI. CONCLUSION: The finding of periventricular cysts in antenatal ultrasound should lead to a reference ultrasound, a key procedure for distinguishing between SEPC and FHC. In our study, no additional benefit from MRI and TFU was established for the evaluation of FHC. These findings should be considered as normal variants, thus limiting pre- and postnatal investigations. The visualization of SEPC, THC, or a parenchymal abnormality on the reference ultrasound should lead to an additional MRI being performed and a personalized follow-up of the child.

Translation and validation of the French version of the ObsQoR-10 questionnaire for the evaluation of recovery after delivery: the ObsQoR-10-French.

Background: The Obstetric Quality of Recovery-10 (ObsQoR-10) is a validated tool for assessing the quality of postpartum recovery. This study aimed to validate the French version of the ObsQoR-10 scale (ObsQoR-10-French). Methods: After translating the ObsQoR-10 into French, we conducted a psychometric validation involving internal consistency, convergent validity, construct validity, reliability, responsiveness, scaling properties, acceptability, and feasibility. French women who underwent either a vaginal delivery (spontaneous or induced labour), or an emergency or elective Caesarean section (C-section) were prospectively included. They completed the ObsQoR-10-French before delivery and at 24 h (H24) and 48 h (H48) after delivery. Results: Of the 500 women included, 431 (86%) completed the questionnaire at all three timepoints. A total of 352 women (82%) underwent vaginal delivery (with 228 [53%] experiencing spontaneous labour and 124 [29%] had labour induced), whereas 53 (12%) women underwent an emergency C-section and 26 (6%) an elective C-section. The ObsQoR-10-French demonstrated excellent internal consistency with a Cronbach's coefficient of 0.81, 95% confidence interval 0.78-0.84 at H24. The tool was correlated with an 11-item global health score (P<0.001). Of the list of hypotheses for evaluating the construct validity, 81% were confirmed (negative associations between ObsQoR-10-French and length of labour, hospital stay, the need for a C-section, and the emergency level of the C-section). The Cohen effect size at H24 was 0.58. The intra-class coefficient was 0.90, 95% confidence interval 0.86-0.93 at H24. Conclusion: The ObsQoR-10-French is a valid and reliable psychometric questionnaire, capable of assessing the quality of postpartum recovery in French-speaking populations. Clinical trial registration: NCT04489602.

Assisted reproductive techniques do not impact late neurodevelopmental outcomes of preterm children.

Objective: Assisted reproductive technology (ART) increases the rate of preterm births, though few studies have analyzed outcomes for these infants. No data are available on 4-year-old children born prematurely after ART. The objective was to investigate whether ART affect the neurodevelopmental outcomes at 4 years in preterm infants born before 34 weeks of gestational age (GA). Methods and results: A total of 166 ART and 679 naturally conceived preterm infants born before 34 weeks GA between 2013 and 2015 enrolled in the Loire Infant Follow-up Team were included. Neurodevelopment was assessed at 4 years using the age and stage questionnaire (ASQ) and the need for therapy services. The association between the socio-economic and perinatal characteristics and non-optimal neurodevelopment at 4 years was estimated. After adjustment, the ART preterm group remained significantly associated with a lower risk of having at least two domains in difficulty at ASQ: adjusted odds ratio (aOR) 0.34, 95% confidence interval (CI) (0.13-0.88), p = 0.027. The factors independently associated with non-optimal neurodevelopment at 4 years were male gender, low socio-economic level, and 25-30 weeks of GA at birth. The need for therapy services was similar between groups (p = 0.079). The long-term neurodevelopmental outcomes of preterm children born after ART are very similar, or even better than that of the spontaneously conceived children.

A Metabolomic Profile of Seminal Fluid in Extremely Severe Oligozoopermia Suggesting an Epididymal Involvement.

Male infertility has increased in the last decade. Pathophysiologic mechanisms behind extreme oligospermia (EO) are not yet fully understood. In new "omics" approaches, metabolomic can offer new information and help elucidate these mechanisms. We performed a metabolomics study of the seminal fluid (SF) in order to understand the mechanisms implicated in EO. We realized a targeted quantitative analysis using high performance liquid chromatography and mass spectrometry to compare the SF metabolomic profile of 19 men with EO with that of 22 men with a history of vasectomy (V) and 20 men with normal semen parameters (C). A total of 114 metabolites were identified. We obtained a multivariate OPLS-DA model discriminating the three groups. Signatures show significantly higher levels of amino acids and polyamines in C group. The sum of polyunsaturated fatty acids and free carnitine progressively decrease between the three groups (C > EO > V) and sphingomyelins are significantly lower in V group. Our signature characterizing EO includes metabolites already linked to infertility in previous studies. The similarities between the signatures of the EO and V groups are clear evidence of epididymal dysfunction in the case of testicular damage. This study shows the complexity of the metabolomic dysfunction occurring in the SF of EO men and underlines the importance of metabolomics in understanding male infertility.

Influence of Diminished Ovarian Reserve on Early Embryo Morphokinetics during In Vitro Fertilization: A Time-Lapse Study.

There is great controversy as to whether women with Diminished Ovarian Reserve (DOR) exhibit only a quantitative decrease in ovarian reserve or also impaired oocyte and embryo quality. In this retrospective study, we aimed to evaluate the impact of DOR on embryo morphokinetic parameters with a time-lapse system. 1314 embryos were obtained from 256 couples undergoing IVF or ICSI cycles, with 242 embryos in the DOR group as classified by the Bologna and POSEIDON criteria and 1072 embryos derived from the Normal Ovarian Reserve (NOR) group. For each morphokinetic parameter (t2, t3, t4, t5, t8, tB, ECC2, cc2a, ECC3, s2, s3), a generalized linear mixed model was created to control for female age, BMI, smoking status, method of insemination and correlation between oocytes from a same cohort. No significant association was found between DOR and any of the morphokinetic parameters studied. In a secondary analysis, we evaluated the influence of maternal aging, comparing morphokinetic characteristics between two age groups (<37 and ≥37 years). In the univariate analysis, we found that embryos from older women displayed a slower embryo development (in particular for t3, t4, t5, tB, and ECC2), although without statistical significance in the multivariate analysis. In conclusion, our study did not reveal any substantial impact of ovarian aging on early morphokinetic parameters and suggested potential biases that may be a source of controversy in the literature.

The role of peak serum estradiol level in the prevention of multiple pregnancies in gonadotropin stimulated intrauterine insemination cycles.

The objective was to assess whether the measurement of serum estradiol (E2) level on trigger day in controlled ovarian stimulation with intrauterine insemination (COS-IUI) cycles helps lower the multiple pregnancy (MP) rate. We performed a unicentric observational study. We included all patients who underwent COS-IUI and had a subsequent clinical pregnancy (CP) between 2011 and 2019. Our main outcome measure was the area under Receiver-Operating Characteristic (ROC) curve. We included 455 clinical pregnancies (CP) obtained from 3387 COS-IUI cycles: 418 singletons, 35 twins, and 2 triplets. The CP, MP, and live birth rates were respectively 13.4%, 8.1% and 10.8%. The area under ROC curve for peak serum E2 was 0.60 (0.52-0.69). The mean E2 level was comparable between singletons and MP (260.1 ± 156.1 pg/mL vs. 293.0 ± 133.4 pg/mL, p = 0.21, respectively). Univariate and multivariate logistic regression analysis showed that E2 level was not predictive of MP rate (aOR: 1.13 (0.93-1.37) and 1.06 (0.85-1.32), respectively). Our study shows that, when strict cancelation criteria based on the woman's age and follicular response on ultrasound are applied, the measurement of peak serum E2 levels does not help reduce the risk of MP in COS-IUI cycles.

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome. METHODS: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076. FINDINGS: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia. INTERPRETATION: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction. FUNDING: French Ministry of Health.

Late fetal demise, a risk factor for post-traumatic stress disorder.

Late-term fetal demise including fetal death in utero, late miscarriage and late termination of pregnancy are relatively frequent occurrences. Post-traumatic stress disorder (PTSD) is a pathology that finds its roots in exposure to a life-threatening event or an event related to death. Exposure to fetal death during a late-term fetal demise is, therefore, a situation at risk of trauma. The objective of this study was to assess the prevalence of PTSD symptoms in the short term among patients faced with late fetal demise, and to identify potential risk factors. All women were assessed at 15 days, one month, and three months after late fetal demise using the Impact of Event Scale-Revised (IES-R) and the Peritraumatic Dissociative Experiences Questionnaire (PDEQ). At 15 days, 44.2% of patients presented a pathological score on the IES-R (≥ 33). At one month and three months, this figure was 34.1% and 9.1% respectively. Factor associated with PTSD symptoms were: peritraumatic dissociation (p = 0.014), seeing the fetus during hospitalization (p = 0.035), holding the fetus in one's arms (p = 0.046), and the organization of a funeral service (p = 0.025). Patients experiencing late fetal demise are at significant risk of trauma. Care providers should remain vigilant to identify high-risk situations to offer appropriate care.Clinical trials registration number: NCT03433989.

Neurodevelopment at 5 years of age for preterm-born children according to mode of conception: a cohort study.

BACKGROUND: Preterm delivery is a risk factor for suboptimal neurodevelopment. Pregnancies conceived after medically assisted reproduction-which includes in vitro fertilization, with or without intracytoplasmic insemination, and induction of ovulation followed by intrauterine insemination or timed intercourse-have a higher risk of preterm delivery. Few studies have evaluated the outcome at >2 years of age of such preterm-born children. OBJECTIVE: To evaluate neurodevelopmental outcome at 5½ years of age of children born preterm according to the mode of conception (spontaneous vs medically assisted reproduction). STUDY DESIGN: A total of 4349 children born between 24 and 34 weeks of gestation who survived to 5½ years of age in the 2011 French prospective national cohort study "EPIPAGE-2" were included: 814 in the medically assisted reproduction group (433 by in vitro fertilization, with or without intracytoplasmic insemination, and 381 by induction of ovulation) and 3535 in the spontaneously conceived group. The studied neurodevelopmental outcomes were sensory (hearing and vision) impairments, cerebral palsy, cognition, and developmental coordination disorders. Multivariate analyses were performed with generalized estimating equation models adjusted for gestational age, antenatal steroids, and social characteristics. All analyses were performed following multiple imputation. Sensitivity analyses were performed with the populations of singletons and cases with complete data. RESULTS: No differences in cerebral palsy (adjusted odds ratio, 1.00; 95% confidence interval, 0.67-1.49), neurodevelopmental impairment (adjusted odds ratio, 1.09; 95% confidence interval, 0.82-1.45), or developmental coordination disorders (adjusted odds ratio, 0.75; 95% confidence interval, 0.50-1.12) were found between children born following medically assisted reproduction and children born following spontaneous conception after adjustment for sociodemographic factors. For proportions of children with an intelligence quotient below 1 and 2 standard deviations, there were no differences between those born after medically assisted reproduction and those born after spontaneous pregnancy (respectively, adjusted odds ratio, 0.99; 95% confidence interval, 0.80-1.23 and adjusted odds ratio, 1.14; 95% confidence interval, 0.83-1.56). In subgroup analyses, no differences were observed between children born following induction of ovulation or in vitro fertilization and those conceived spontaneously. Sensitivity analyses were consistent with the main results. CONCLUSION: In this cohort of preterm-born children, there was no evidence of an impact of the mode of conception on neurodevelopmental outcomes at 5½ years of age.

Management of non-tubal ectopic pregnancies in France: Results of a practice survey.

INTRODUCTION: Non-tubal ectopic pregnancies (NTEP) in France constitute approximately 5% of ectopic pregnancies (EP). A NTEP can be abdominal, ovarian, cervical, interstitial, on a caesarean scar, or cornual. These pregnancies, which are sometimes difficult to diagnose and are often diagnosed late, carry a high risk of complications, particularly haemorrhages. Many treatments have been described for treating these NTEP. Our objective is to assess how they are cared for in terms of diagnosis, treatment and monitoring. EQUIPMENT AND METHODOLOGY: An online questionnaire was sent out to all members of the French Society of gynecologic and Pelvic Surgery (SCGP) in September 2020. The questionnaire was in the form of two clinical cases on interstitial and caesarean scar pregnancies. RESULTS: 141 SCGP members responded (36%). For diagnosis, 58% of respondents enlisted the help of a specialist sonographer. MRI is rarely used for diagnosis to the extent that it was only requested in 7% of cases for interstitial pregnancy and 23.6% of cases for caesarean scar pregnancy. In the case of stable interstitial pregnancy without signs of complications, treatment is predominantly medical (90%), with the use of methotrexate (MTX) by intramuscular injection in 33.3% of cases, by in situ injection in 30.7% of cases, or a combination of the two in 36% of cases. If there were signs of pre-rupture, the majority of respondents performed laparoscopic surgical treatment (79.3%). In terms of caesarean scar pregnancies, the treatment was predominantly medical (78.2%) with the use of MTX only, as an intramuscular injection in 23.3% of cases, in situ in 36% of cases, and as a combination of intramuscular and in situ in 37.2% of cases. DISCUSSION: Non-tubal ectopic pregnancies are sometimes difficult to diagnose in the first trimester and constitute a significant haemorrhage risk for patients. In France, there is currently no specific recommendation on this subject and there is huge disparity in practice.

Efficacy of In Situ Methotrexate Injection in the Treatment of Nontubal Ectopic Pregnancies: A Retrospective Multicenter Study.

STUDY OBJECTIVE: Evaluation of the efficacy of different injection sites of methotrexate in the treatment of nontubal ectopic pregnancies. DESIGN: Retrospective multicenter study. SETTING: Multicenter, including 3 teaching hospitals, an intercommunal hospital, and a clinic. PATIENTS: A total of 106 patients with nontubal ectopic pregnancies, including 59 interstitial, 39 cesarean scar, and 8 cervical or isthmic. INTERVENTIONS: Overall, 58 patients received methotrexate via intramuscular injection (IM group), 35 received methotrexate via in situ injection (IS group), and 13 received a combination of both in situ and intramuscular injections of methotrexate (IS + IM group). MEASUREMENTS AND MAIN RESULTS: The main end point of this study was measured via the primary success rate (defined as a negative ß-human chorionic gonadotropin level without recourse to any additional treatment) of treatment with methotrexate according to injection site. The primary success rate was 46.55% in the IM group, 60% in the IS group, and 61.54% in the IS + IM group, respectively. In the multivariate analysis, the primary success rate of treatment was significantly correlated to the in situ injection of methotrexate, either solely or in conjunction with an intramuscular injection of methotrexate administered the following day, (odds ratio = 2.7; 95% confidence interval, 1.03-7.14). CONCLUSION: Solely an intramuscular injection of methotrexate is a less efficient first-line treatment strategy for the conservative management of nontubular ectopic pregnancy. The use of an in situ injection of methotrexate should therefore be preferred.

Change in the Strategy of Embryo Selection with Time-Lapse System Implementation-Impact on Clinical Pregnancy Rates.

Time-lapse systems (TLS) and associated algorithms are interesting tools to improve embryo selection. This study aimed to evaluate how TLS and KIDScore™ algorithm changed our practices of embryo selection, as compared to a conventional morphological evaluation, and improved clinical pregnancy rates (CPR). In the study group (year 2020, n = 303 transfers), embryos were cultured in an EmbryoScope+ time-lapse incubator. A first team observed embryos conventionally once a day, while a second team selected the embryos for transfer based on time-lapse recordings. In the control group (year 2019, n = 279 transfers), embryos were selected using the conventional method, and CPR were recorded. In 2020, disagreement between TLS and the conventional method occurred in 32.1% of transfers, more often for early embryos (34.7%) than for blastocysts (20.5%). Irregular morphokinetic events (direct or reverse cleavage, multinucleation, abnormal pronuclei) were detected in 54.9% of the discordant embryos. When it was available, KIDScore™ was decreased for 73.2% of the deselected embryos. Discordant blastocysts mainly corresponded with a decrease in KIDScore™ (90.9%), whereas discordant Day 3 embryos resulted from a decreased KIDScore™ and/or an irregular morphokinetic event. CPR was significantly improved in the TLS group (2020), as compared to the conventional group (2019) (32.3% vs. 21.9%, p = 0.005), even after multivariate analysis. In conclusion, TLS is useful to highlight some embryo development abnormalities and identify embryos with the highest potential for pregnancy.

Use of artificial intelligence to predict mean time to delivery following cervical ripening with dinoprostone vaginal insert.

OBJECTIVE: To validate a mathematical model to predict the mean time to delivery (TTD) following cervical ripening with dinoprostone vaginal insert (DVI), and assess its impact on the risk of nocturnal deliveries. METHODS: We performed a case-control retro-prospective study at Angers University Hospital. In the control group, we retrospectively included 405 patients who underwent cervical ripening with DVI between 01/2015 and 09/2016. Based on the delivery outcomes, we developed a mathematical model that integrates all the factors influencing TTD following cervical ripening with DVI. In the study group, we prospectively included 223 patients who underwent cervical ripening with DVI between 11/2017 and 11/2018. The timing of insertion was calculated using the mathematical model developed in the control group, in order to prevent the occurrence of nocturnal deliveries. RESULTS: The calculated mean TTD was significantly shorter than the real mean TTD (21h46 min ± 3h28 min versus 25h38 min ± 12h10 min, p < 0.001), and for 44% of patients, there was at least 10 h difference between the two. The real TTD (25h38 min ± 12H10 min versus 20h39 min ± 10h49, p < 0.001), and the rate of nocturnal deliveries (30.5% versus 21.2%, p = 0.01) were significantly higher in the study group compared to the control group. CONCLUSION: The mathematical model did not help predicting TTD following cervical ripening with DVI, and or reducing the number of nocturnal deliveries.

Prophylactic procedures associated with gynecological surgery for the management of superficial endometriosis and adhesions. Clinical practice guidelines from the French College of Gynecologists and Obstetricians (CNGOF)✰.

OBJECTIVE: To provide guidelines from the French College of Obstetricians and Gynecologists (CNGOF), based on the best currently available evidence, for the prophylactic procedures associated with gynecological surgery for benign disease such as superficial endometriosis lesions and adhesions. METHODS: The CNGOF has decided to adopt the AGREE II and GRADE systems for grading scientific evidence. Each recommendation for practice was allocated a grade that reflects the quality of evidence (QE) (clinical practice guidelines). RESULTS: Endometriosis and pelvic pain Superficial endometriosis can be entirely asymptomatic. Surgical treatment of asymptomatic superficial peritoneal endometriosis is not recommended in women of childbearing age for the prevention of pelvic pain, especially in case of proximity to noble organs (e.g., the ureters, rectum and sigmoid, and ovaries in nulligravida) as there is no evidence that the disease will progress to become symptomatic (low level of evidence). In case of accidental discovery of superficial endometriosis in women of childbearing age with pelvic pain, it is recommended that the lesions are excised, if surgically accessible. Removal of superficial endometriosis lesions in patients with painful symptoms improves quality of life and pain (low level of evidence). Endometriosis and infertility It appears that women with isolated superficial endometriosis diagnosed by laparoscopy with histological confirmation have a significantly higher incidence of primary infertility than patients without endometriosis. However, there is no data regarding the impact of treatment of these lesions on the fertility in these women or on the natural course of their disease (low level of evidence). It is recommended that excision is performed rather than monopolar coagulation of superficial endometriosis lesions in infertile women, as this results in a higher spontaneous pregnancy rate (low level of evidence). Adhesions and pelvic pain There is limited data in the literature regarding the benefit of performing systematic adhesiolysis during laparoscopy to prevent pelvic pain when incidental pelvic adhesions are discovered. For patients with pelvic pain, it is probably better not to perform adhesiolysis to prevent pelvic pain, although this can be decided on a case-by-case basis depending on the extent of the adhesions, the topography, and the type of surgery considered (low level of evidence). For asymptomatic patients, it is recommended not to perform adhesiolysis to prevent pelvic pain due to the lack of clear efficacy both short- or long-term and due to the increased risk of surgical injuries (low level of evidence). Adhesions and infertility There is limited data in the literature regarding the potential benefit of performing systematic adhesiolysis when there is an incidental discovery of pelvic adhesions during laparoscopy to prevent infertility. For infertile women, in the event of fortuitous discovery of adhesions at laparoscopy, it is probably better not to perform complex adhesiolysis. Only adhesiolysis of tubo-ovarian adhesions that are minimal or slight in terms of their extension and/or their nature may be useful to improve the chances of spontaneous pregnancy. However, it remains to be decided on a case-by-case basis depending on other potential causes of infertility (low level of evidence). For women without known infertility issues, it is probably better not to perform systematic adhesiolysis in order to improve their pregnancy chances, considering the balance between the unknown benefit and the risks of complications inherent to surgery (low level of evidence). CONCLUSION: Further investigations are needed in order to increase the quality of management regarding associated interventions such as the treatment of superficial endometriosis or adhesions performed during a gynecologic surgical procedure and, thereby, bolster these recommendations.

Impact of the type of endometrial oestrogen preparation for frozen-thawed embryo (vaginal or transdermal) on perinatal outcomes in an artificial cycle.

INTRODUCTION: Serum oestradiol concentration at the time of frozen embryo transfer (FET) in artificial cycle are lower when using transdermal administration of oestrogen for endometrial preparation compared to the vaginal route. This difference could have consequences for placentation and establishment of maternal-foetal circulation. The aim of our study was to compare the birth weight of newborns and the perinatal issues after FET in an artificial cycle with regard to the route of administration of oestrogens. METHODS: Retrospective monocentric cohort study in the medically assisted reproduction department of the University Hospital of Angers, France, between January 2017 and October 2020. Inclusion criteria were age >18 years old and one live birth after FET in an artificial cycle. The main outcome was the birth weight of the newborns. The choice of oestrogens administration (transdermal or vaginal) was left to the patient. RESULTS: 804 FET in artificial cycle were included in our study. Oestrogens were administrated in 356/804(36.6%) patients using transdermal route and in 448/804(45.9%) patients using vaginal route. There were 68/345 (19.1%) live births in the transdermal group and 85/448 (19%) in the vaginal group. There was no difference in the birth weight of the newborns (3320[2100-4165] grams in the transdermal group vs 3327.5[915-4650] grams in the vaginal group, p=0.72). All the other perinatal issues were comparable between the two groups. CONCLUSION: Birth weights and perinatal issues were comparable with regard to the route of administration of oestrogens (vaginal or transdermal) in the context of endometrial preparation before FET in an artificial cycle.

Delivery Mode After Manual Rotation of Occiput Posterior Fetal Positions: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether manual rotation of fetuses in occiput posterior positions at full dilation increases the rate of spontaneous vaginal delivery. METHODS: In an open, single-center, randomized controlled trial, patients with a term, singleton gestation, epidural analgesia, and ultrasonogram-confirmed occiput posterior position at the start of the second stage of labor were randomized to either manual rotation or expectant management. Our primary endpoint was the rate of spontaneous vaginal delivery. Secondary endpoints were operative vaginal delivery, cesarean delivery, and maternal and neonatal morbidity. Analyses were based on an intention-to-treat method. A sample size of 107 patients per group (n=214) was planned to detect a 20% increase in the percent of patients with a spontaneous vaginal delivery (assuming 60% without manual rotation vs 80% with manual rotation) with 90% power and alpha of 0.05. RESULTS: Between February 2017 and January 2020, 236 patients were randomized to either manual rotation (n=117) or expectant management (n=119). The success rate of the manual rotation maneuver, defined by conversion to an anterior position as confirmed by ultrasonogram, was 68%. The rate of the primary endpoint did not differ between the groups (58.1% in manual rotation group vs 59.7% in expectant management group (risk difference -1.6; 95% CI -14.1 to 11.0). Manual rotation did not decrease the rate of operative vaginal delivery (29.9% in manual rotation group vs 33.6% in expectant management group (risk difference -3.7; 95% CI -16.6 to 8.2) nor the rate of cesarean delivery (12.0% in manual rotation group vs 6.7% in expectant management group (risk difference 5.3; 95% CI -2.2 to 12.6). Maternal and neonatal morbidity was also similar across the two groups. CONCLUSION: Manual rotation of occiput posterior positions at the start of second stage of labor does not increase the rate of vaginal delivery without instrumental assistance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03009435.

Mitochondria: their role in spermatozoa and in male infertility.

BACKGROUND: The best-known role of spermatozoa is to fertilize the oocyte and to transmit the paternal genome to offspring. These highly specialized cells have a unique structure consisting of all the elements absolutely necessary to each stage of fertilization and to embryonic development. Mature spermatozoa are made up of a head with the nucleus, a neck, and a flagellum that allows motility and that contains a midpiece with a mitochondrial helix. Mitochondria are central to cellular energy production but they also have various other functions. Although mitochondria are recognized as essential to spermatozoa, their exact pathophysiological role and their functioning are complex. Available literature relative to mitochondria in spermatozoa is dense and contradictory in some cases. Furthermore, mitochondria are only indirectly involved in cytoplasmic heredity as their DNA, the paternal mitochondrial DNA, is not transmitted to descendants. OBJECTIVE AND RATIONAL: This review aims to summarize available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility. SEARCH METHODS: PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews pertaining to human spermatozoa and mitochondria. Searches were performed using keywords belonging to three groups: 'mitochondria' or 'mitochondrial DNA', 'spermatozoa' or 'sperm' and 'reactive oxygen species' or 'calcium' or 'apoptosis' or signaling pathways'. These keywords were combined with other relevant search phrases. References from these articles were used to obtain additional articles. OUTCOMES: Mitochondria are central to the metabolism of spermatozoa and they are implicated in energy production, redox equilibrium and calcium regulation, as well as apoptotic pathways, all of which are necessary for flagellar motility, capacitation, acrosome reaction and gametic fusion. In numerous cases, alterations in one of the aforementioned functions could be linked to a decline in sperm quality and/or infertility. The link between the mitochondrial genome and the quality of spermatozoa appears to be more complex. Although the quantity of mtDNA, and the existence of large-scale deletions therein, are inversely correlated to sperm quality, the effects of mutations seem to be heterogeneous and particularly related to their pathogenicity. WIDER IMPLICATIONS: The importance of the role of mitochondria in reproduction, and particularly in gamete quality, has recently emerged following numerous publications. Better understanding of male infertility is of great interest in the current context where a significant decline in sperm quality has been observed.