Estimation of the prevalence of uterine infertility and its different causes in France according to data from a literature review.

INTRODUCTION: Uterine infertility (UI) is defined as the complete absence of a uterus (absolute uterine infertility or AUI) or the presence of a non functional uterus (non-absolute uterine infertility or NAUI). The exact prevalence of uterine infertility is currently unknown. Our aim was to assess the number of French women concerned by Uterine Infertility according to a recent literature review. MATERIALS AND METHODS: We have previously conducted a systematic review of the literature on UI and its various causes in the world. Based on these study and demographic data of 2022 from INSEE (Institut National de la Statistique et des Études Économiques), we attempted to estimate the number of women under 40 years of age in France affected by potential UI using direct standardization. RESULTS AND DISCUSSION: Based on the estimation from INSEE data, approximately 2066 women of childbearing age would have MRKH syndrome in France, 380 the Androgen Insensitivity Syndrome and 3700 had an haemostasis hysterectomy in France. We did not find data on the prevalence of hysterectomies before the age of 40 in France. For the following pathologies: uterine malformations, radiation uterus, synechiae, myomas and adenomyosis there was a huge amount of missing data, which does not allow us to estimate the number of potentially infertile patients. CONCLUSION: Prevalence of UI is poorly known. UI probably concerns several thousand patients in France. The creation of a UI registry would make enable to assess the number of patients potentially eligible for adoption, uterus transplantation or even surrogacy.

Use of uterine manipulator and uterine perforation in minimally invasive endometrial cancer surgery.

OBJECTIVE: Safety of the uterine manipulator (UM) within endometrial cancer (EC) surgery is being questioned. Its use might be one of the issues for potential tumor dissemination during the procedure, especially in the case of uterine perforation (UP). No prospective data on this surgical complication, nor on the oncological consequences exist. The aim of this study was to assess the rate of UP while using UM when performing surgery for EC and the impact of UP on the choice of adjuvant treatment. METHODS: We conducted a prospective single-center cohort study from November 2018 to February 2022, considering all EC cases surgically treated by a minimally invasive approach with the help of a UM. Demographic, preoperative, postoperative and adjuvant treatment corresponding to the included patients were collected and comparatively analyzed according to the absence or presence of a UP. RESULTS: Of the 82 patients included in the study, 9 UPs (11%) occurred during surgery. There was no significant difference in demographics and disease characteristics at diagnosis that may have induced UP. The type of UM used or the approach (laparoscopic vs. robotic) did not influence the occurrence of UP (p = 0.44). No positive peritoneal cytology was found post hysterectomy. There was a statistically significantly higher rate of lymph-vascular space invasion within the perforation group, 67% vs. 25% in the no perforation group, p = 0.02. Two out of nine (22%) adjuvant therapies were changed because of UP. The median follow-up time for patients was 7.6 months (range 0.5-33.1 months). No recurrence was found in the UP group. CONCLUSION: Our study found a uterine perforation rate of 11%. This information needs to be further integrated to consider the usefulness of MU for EC surgery.

Borderline ovarian tumors: Guidelines from the French national college of obstetricians and gynecologists (CNGOF).

It is recommended to classify Borderline Ovarian Tumors (BOTs) according to the WHO classification. Transvaginal and suprapubic ultrasonography are recommended for the analysis of an ovarian mass (Grade A). In case of an undetermined ovarian lesion on ultrasonography, it is recommended to perform a pelvic MRI (Grade A) with a score for malignancy (ADNEX MR/O-RADS) (Grade C) included in the report and to formulate a histological hypothesis (Grade C). Pelvic MRI is recommended to characterize a tumor suspected of being BOT (Grade C). It is recommended to evaluate serum levels of HE4 and CA125 and to use the ROMA score for the diagnosis of indeterminate ovarian mass on imaging (grade A). If there is a suspicion of a mucinous BOT on imaging, serum levels of CA 19-9 may be proposed (Grade C). For Early Stages (ES) of BOT, if surgery without risk of tumor rupture is possible, laparoscopy with protected extraction is recommended over laparotomy (Grade C). For treatment of a bilateral serous ES BOT with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended where possible (Grade B). For mucinous BOTs with a treatment strategy of fertility and/or endocrine function preservation, unilateral salpingo-oophorectomy is recommended (grade C). For mucinous BOTs treated by initial cystectomy, unilateral salpingo-oophorectomy is recommended (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). For ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only in case of a macroscopically pathological appendix (Grade C). Restaging surgery is recommended in cases of serous BOTs with micropapillary architecture and an incomplete abdominal cavity inspection during initial surgery (Grade C). Restaging surgery is recommended for mucinous BOTs after initial cystectomy or in cases where the appendix was not examined (Grade C). If restaging surgery is decided for ES BOTs, the following procedures should be performed: peritoneal washing (grade C), omentectomy (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix and appendectomy in case of a pathological macroscopic appearance (grade C) as well as unilateral salpingo-oophorectomy in case of a mucinous BOT initially treated by cystectomy (grade C). In advanced stages (AS) of BOT, it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). For AS BOT in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed (Grade C). Restaging surgery aimed at removing all lesions, not performed initially, is recommended for AS BOTs (Grade C). After treatment, follow-up for a duration greater than 5 years is recommended due to the median recurrence time of BOTs (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). If the determination of tumor markers is normal preoperatively, the routine dosage of tumor markers in BOT follow-up is not recommended (Grade C). In case of an initial elevation in serum CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In case of conservative treatment, it is recommended to use transvaginal and transabdominal ultrasound during follow up of a treated BOT (Grade B). In the event of a BOT recurrence in a woman of childbearing age, a second conservative treatment may be proposed (Grade C). A consultation with a physician specialized in Assisted Reproductive Technique (ART) should be offered in the case of BOTs in women of childbearing age (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). In the case of optimally treated BOT, there is no evidence to contraindicate the use of ART. The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After management of mucinous BOT, for women under 45 years, given the benefit of Hormonal Replacement Therapy (HRT) on cardiovascular and bone risks, and the lack of hormone sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). Over 45 years of age, HRT can be prescribed in case of a climacteric syndrome after individual benefit to risk assessment (Grade C).

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Diagnosis and Management of Recurrent Borderline Ovarian Tumours]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Diagnostic et prise en charge des récidives.

OBJECTIVE: To provide recommendations for the diagnosis and management of the recurrence of Borderline Ovarian Tumour (BOT). METHODS: Literature review by consulting Pubmed, Medline and Cochrane databases. RESULTS: In the case of BOT, most of recurrences are a new BOT without invasive contingent (LE2). In the case of bilateral BOT, bilateral cystectomy is associated with a shorter recurrence time compared to unilateral oophorectomy and contralateral cystectomy (LE2). In recurrent serous BOT, cysts are usually fluid thin-walled with vegetation, corresponding in the IOTA classification to a solid unilocular cyst (LE2). A size of the cyst less than 20mm is not a sufficient to eliminate the diagnosis of recurrent serous BOT (LE2). Recurrence of mucinous BOT predominantly appears as multilocular or as solid multilocular cysts (LE4). In the case of ovarian preservation, recurrences are most often observed on the preserved ovary(s) (LE2). Non-invasive peritoneal recurrence after initial radical treatment including bilateral hysterectomy and adnexectomy is possible, mainly in patients initially diagnosed with stage II or III BOT with non-invasive peritoneal implant (LE3). Most BOT recurrences are asymptomatic, but clinical examination may allow diagnosis of recurrence (LE2). The normality of the CA 125 dosage does not rule out the diagnosis of recurrent BOT (LE2). A second conservative treatment in the event of recurrence of BOT entails the risk of new recurrence (LE2) with no impact on survival (LE4). Totalization of the adnexectomy in case of recurrence of BOT reduces the risk of new recurrence (LE2). Conservative treatment does not increase the risk of recurrence with non-invasive peritoneal implants (LE4). Conservative treatment may be offered after a first non-invasive recurrence in young women who wish to preserve their fertility (gradeC). In the absence of infiltrating tumor, chemotherapy is not indicated. The only cases for which chemotherapy can be considered are those for which there is an infiltrative component in addition to TFO.

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Short Text]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C).

[Borderline Ovarian Tumours: CNGOF Guidelines for Clinical Practice - Epidemiology and Risk Factors of Relapse, Follow-up and Interest of a Completion Surgery]. / Tumeurs frontières de l'ovaire. Recommandations pour la pratique clinique du CNGOF ­ Épidémiologie et facteurs de risques de récidive, modalités de surveillance et intérêt d'une chirurgie de clôture.

OBJECTIVE: To provide clinical practice guidelines from the French college of obstetrics and gynecology (CNGOF) based on the best evidence available, concerning epidemiology of recurrence, the risk or relapse and the follow-up in case of borderline ovarian tumor after primary management, and evaluation of completion surgery after fertility sparing surgery. MATERIAL AND METHODS: English and French review of literature from 2000 to 2019 based on publications from PubMed, Medline, Cochrane, with keywords borderline ovarian tumor, low malignant potential, recurrence, relapse, follow-up, completion surgery. From 2000 up to this day, 448 references have been found, from which only 175 were screened for this work. RESULTS AND CONCLUSION: Overall risk of recurrence with Borderline Ovarian Tumour (BOT) may vary from 2 to 24% with a 10-years overall survival>94% and risk of invasive recurrence between 0.5 to 3.8%. Age<40 years (level of evidence 3), advanced initial FIGO stage (LE3), fertility sparing surgery (LE2), residual disease after initial surgery for serous BOT (LE2), implants (invasive or not) (LE2) are risk factors of recurrence. In case of conservative treatment, serous BOT had a higher risk of relapse than mucinous BOT (LE2). Lymphatic involvement (LE3) and use of mini invasive surgery (LE2) are not associated with a higher risk of recurrence. Scores or Nomograms could be useful to assess the risk of recurrence and then to inform patients about this risk (gradeC). In case of serous BOT, completion surgery is not recommended, after conservative treatment and fulfillment of parental project (grade B). It isn't possible to suggest a recommendation about completion surgery for mucinous BOT. There is not any data to advise a frequency of follow-up and use of paraclinic tools in general case of BOT. Follow-up of treated BOT must be achieved beyond 5 years (grade B). A systematic clinical examination is recommended during follow-up (grade B), after treatment of BOT. In case of elevation of CA-125 at diagnosis use of CA-125 serum level is recommended during follow-up of treated BOT (grade B). When a conservative treatment (preservation of ovarian pieces and uterus) of BOT is performed, endovaginal and transabdominal ultrasonography is recommended during follow-up (grade B). There isn't any sufficient data to advise a frequency of these examinations (clinical examination, ultrasound and CA-125) in case of treated BOT. CONCLUSION: Risk of relapse after surgical treatment of BOT depends on patients' characteristics, type of BOT (histological features) and modalities of initial treatment. Scores and nomogram are useful tools to assess risk of relapse. Follow-up must be performed beyond 5 years and in case of peculiar situations, use of paraclinic evaluations is recommended.

[External validation of FullPIERS model for prediction of adverse outcomes among women with pre-eclampsia in French maternity of 2014 to 2018]. / Validation externe du modele FullPIERS dans la pré-éclampsie à partir d'une série française de 4 ans.

OBJECTIVES: FullPIERS score (Pre-eclampsia Integrated Estimate of RiSk) is built in order to predict maternal outcomes among women with preeclampsia. Our objective is to assess external validity of this score among a population of French women. METHODS: A retrospective study was conducted for all patients with pre-eclampsia (severe or not) admitted to a tertiary hospital center. A receiver operating characteristic (ROC) curve was constructed to determine accuracy of the model at 48 hours and 7 days after admittance and area under the curve (AUC) was calculated. RESULTS: In total, 276 patients meet inclusions criterion. Among them, 217 were included and 61 (28 %) had one or more complication. Only 8 patients had two complications at two different moments (one at 48 hours and one at 7 days). The FullPiers score predicted maternels events at 48 hours with an area under the curve at 0.80 (IC95 % [0.74-0.85]). At 4.2 cut off, the sensitivity was 71 % and specifity 88 %. At 7 days, the area under the curve was 0.74 (IC95 % [0.67-0.79]), admiting a cutoff point for FullPIERS probability of 3.4, sensitivity was 59 % and specificity 85 %. CONCLUSIONS: Our study show utility of FullPIERS score in french maternity. This model might be a useful tool for predicting complications in women with pre-eclampsia. Using of this score in clinical practice might help improving optimization of patient's care.

Is there an interest in repeating the vaginal administration of dinoprostone (Propess®), to promote induction of labor of pregnant women at term? (RE-DINO): study protocol for a randomized controlled trial.

BACKGROUND: Labor is induced in over 20% of women in France. Prostaglandins, especially intravaginal dinoprostone (Propess®), are widely used to initiate cervical ripening. If labor does not start within 24 h, there is uncertainty about whether to administer a second dinoprostone pessary or to use oxytocin to induce labor in order to achieve a vaginal delivery. METHODS: RE-DINO is a prospective, open-label, multicenter, randomized superiority trial with two parallel arms running in six French hospitals. A total of 360 patients ≥ 18 years of age at > 37 weeks of gestation who exhibit unfavorable cervical conditions (Bishop score < 6) 24 h after placement of the first Propess®, with fetuses in cephalic presentation, will be included. Patients with premature membrane rupture, uterine scars, or multiple pregnancies will be excluded. Our principal objective is to determine whether placement of a second Propess® (followed by oxytocin [Syntocinon®], if necessary) in women for whom the first Propess® failed to induce cervical ripening increases the vaginal delivery rate compared to direct oxytocin injection. The vaginal delivery rate is therefore the primary outcome. The secondary outcomes are the induction failure rates and maternofetal morbidity and mortality. DISCUSSION: This study may help in determining the optimal way to induce labor after failure of a first Propess®, an unresolved problem to date. This trial explores the effectiveness and safety of placing a second Propess® and may contribute to development of an obstetric consensus. TRIAL REGISTRATION: Registered on 2 September 2016 at clinicaltrials.gov (identification number NCT02888041).

Changes in the metabolic composition of storage solution with prolonged cold ischemia of the uterus.

INTRODUCTION: The development of uterine transplantation (UTx) from deceased donors requires knowledge of the tolerance of the uterus to prolonged cold ischemia (CI). This can be evaluated through the use of biological parameters to assess degradation of the organ between its procurement and transplantation. The objective of this study was to analyze changes in the metabolic composition of the storage solution in cases of prolonged CI in uteri from ewes. METHODS: Eighteen uterine auto-transplantations were performed in ewes. CI time was 1 h (T1) or 24 h (T24). Samples of Celsior® were taken when the explanted uterus was flushed (T0) and at the end of CI. A dual approach to metabolic analyses was followed: targeted biochemical analyses targeting several predefined metabolites and non-targeted metabolomics analyses based on nuclear magnetic resonance (NMR). RESULTS: Metabolic analyses were performed on 16 explanted uteri. Metabolomic profiles differed significantly between T1 and T24 (p = 0.003). Hypoxia-associated degradation of the organ was demonstrated by the significantly higher lactate levels at T24 than at T1 (p < 0.05), accompanied by cell lysis, and significantly higher levels of creatine kinase activity in T24 than in T1 uteri (p < 0.05). Oxidative stress increased over time, with a significantly higher oxidized glutathione/glutathione ratio for T24 than for T1 uteri (p < 0.05). CONCLUSION: The metabolic results indicate a significant degradation of the uterus during 24 h of CI. Metabolic analysis of the storage solution could be used as a non-invasive tool for evaluating uterine degradation during CI before transplantation.

[Risk of axillary recurrence after sentinel lymph node biopsy before neoadjuvant chemotherapy in breast cancer]. / Récidive axillaire après prélèvement du ganglion sentinelle avant chimiothérapie néoadjuvante dans le cancer du sein.

OBJECTIVES: In case of large breast cancer, neoadjuvant chemotherapy (NAC) can be performed to reduce the size of the tumor and thus perform a conservative surgery. The place of the sentinel lymph node biopsy (SLNB) in case of NAC is still debated. The main aim of this study is to assess the risk of axillary recurrence after negative SLNB before NAC. METHODS: It is a retrospective, observational and uni-centric study. We included 18 to 80-year-old patients with unilateral breast cancer requiring a NAC and with a negative SLNB before NAC. Our primary endpoint was axillary recurrence. RESULTS: Between August 2006 and October 2016, 64 patients had a negative GS performing before a NAC and did not benefit from axillary dissection after NAC. The average duration of follow-up was 37 months. During our follow-up, we did not find any cases of axillary recurrence. CONCLUSION: This study supports the reliability of lymph node status assessment using the SLNB before CNA.

Borderline ovarian tumors: french guidelines from the CNGOF. Part 2. Surgical management, follow-up, hormone replacement therapy, fertility management and preservation

In the Early Stages (ES) of Borderline Ovarian Tumor (BOT), if surgery without risk of tumor rupture is possible, then laparoscopy with protected extraction is recommended over laparotomy (Grade C). In case of bilateral serous ES BOT treatment with a strategy to preserve fertility and/or endocrine function, bilateral cystectomy is recommended if possible (Grade B). In case of mucinous BOT treatment with a strategy to preserve fertility and/or endocrine function, unilateral adnexectomy is recommended (grade C). In the case of a mucinous BOT in a patient who has had an initial cystectomy, unilateral adnexectomy is recommended (grade C). In the case of treatment of a serous ES BOT in a patient who has had an initial cystectomy, with a strategy to preserve fertility and/or endocrine function, restaging surgery for adnexectomy is not recommended in the absence of suspicious residual lesions at the time of surgery and/or postoperative imaging (reference ultrasonography or pelvic MRI) (grade C). For serous or mucinous ES BOTs, routine hysterectomy is not recommended (Grade C). In cases of ES BOTs, lymphadenectomy is not recommended (Grade C). For ES BOTs, appendectomy is recommended only if there is a macroscopically pathological aspect to the appendix (Grade C). Restaging surgery is recommended in case of a serous BOT with a micropapillary aspect and an unsatisfactory inspection of the abdominal cavity during initial surgery (Grade C). Restaging surgery is recommended in cases of mucinous BOT if only a cystectomy has been performed or if the appendix has not been evaluated (Grade C). If restaging surgery is decided for an ES BOT, the following procedures should be performed: peritoneal cytology (grade C), omentectomy (there is no data in literature to recommend which type of omentectomy should be performed) (grade B), complete exploration of the abdominal cavity with peritoneal biopsies (grade C), visualization of the appendix +/- appendectomy in case of pathological macroscopic appearance (grade C) and unilateral adnexectomy in case of a mucinous BOT (grade C). In advanced stages of BOT it is not recommended to perform a lymphadenectomy as a routine procedure (Grade C). In cases of an advanced stage BOT, in a patient with a desire to fall pregnant, conservative treatment involving preservation of the uterus and all or part of the ovary may be proposed after a multidisciplinary meeting (Grade C). Second surgery aimed at removing all lesions, if not performed initially, is recommended in cases of advanced stage BOT (Grade C). It is not recommended to perform completion surgery after conservative treatment (preservation of the ovaries and the uterus) and after the achievement of fertility desire for a serous BOT (Grade B). After treatment for a BOT, follow-up beyond 5 years is recommended due to the median time to recurrence (Grade B). It is recommended that a systematic clinical examination be carried out during follow-up of a treated BOT (Grade B). In the particular case of an initial elevation of CA 125 levels, it is recommended to monitor CA 125 during follow up (Grade B). In cases treated conservatively (ovarian and uterine conservation), it is recommended to use endovaginal and transabdominal ultrasonography during the follow up period (Grade B). In the event of a recurrence of a BOT, in a woman of childbearing age, a conservative treatment strategy can again be proposed (Grade C). In the presence of non-invasive BOT implants, conservative treatment may be considered after a first non-invasive recurrence in women who wish to preserve their fertility (Grade C). Pelvic MRI is recommended after 12 weeks of amenorrhea in case of an undetermined adnexal mass and should be concluded with a diagnostic score (Grade C). The injection of gadolinium, in case of pregnancy, should be discussed on a case-by-case basis due to the proven risks for the foetus (Grade C). If feasible, a laparoscopic approach should be preferred during pregnancy (Grade C). A consultation with a specialist reproductive physician should be offered to patients with a BOT and of childbearing age (Grade C). It is recommended that patients be provided with full information on the risk of decreased ovarian reserve following to surgical treatment. It is recommended that the ovarian reserve be evaluated prior to surgical management of a suspected BOT (Grade C). When possible, a conservative surgical strategy is recommended to preserve fertility in women of childbearing age (Grade C). There is no specific data on the management of infertility following to conservative treatment of BOT. In case of durable infertility following to conservative treatment of BOT, a consultation with a specialist reproductive physician is required (Grade C). In the case of optimally treated BOT, there is no evidence in literature to contraindicate the use of Assisted Reproductive Techniques (ART). The use of hormonal contraception after serous or mucinous BOT is not contraindicated (Grade C). After treatment of a mucinous BOT, for women aged under 45 years, given the benefit of hormonal replacement therapy (HRT) on cardiovascular and bone risks, and the lack of hormone-sensitivity of mucinous BOTs, it is recommended to offer HRT (Grade C). After treatment of a mucinous BOT, for women over 45 years of age, there is no argument to contraindicate the use of HRT. HRT can be prescribed in case of a climacteric syndrome, as part of an individual benefit to risk assessment (Grade C).