Tumeurs frontières de l’ovaire. Recommandations pour la pratique clinique du CNGOF – Fertilité

International audienceObjectivesBorderline ovarian tumors (BOT) represent around 15% of all ovarian neoplasms and are more likely tobe diagnosed in women of reproductive age. Overall, given the epidemiological profile of BOT and theirfavourable prognosis, ovarian function and fertility preservation should be systematically considered in patientspresenting these lesions.MethodsThe research strategy was based on the following terms: borderline ovarian tumor, fertility, fertility preservation,infertility, fertility-sparing surgery, in vitro fertilization, ovarian stimulation, oocyte cryopreservation,using PubMed, in English and French.Results and conclusionsFertility counselling should become an integral part of the clinical management of women with BOT. Patientswith BOT should be informed that surgical management of BOT may cause damage ovarian reserveand/or peritoneal adhesions. Nomogram to predict recurrence, ovarian reserve markers and fertility explorationsshould be used to provide a clear and relevant information about the risk of infertility in patients withBOT. Fertility-sparing surgery should be considered for young women who wish preserving their fertilitywhen possible. There is insufficient evidence to claim a causal relation between controlled ovarian stimulation(COS) and BOT. However, in case of poor prognosis factors, the use of COS should be consideredcautiously through a multidisciplinary approach. In case of infertility after surgery for BOT, COS can be performedwithout delay, once histopathological diagnosis of BOT is confirmed. There is insufficient consistentevidence that fertility drugs and COS increase the risk of recurrence of BOT after conservative management.The conservative surgical treatment can be associated to oocyte cryopreservation considering the high riskof recurrence of the disease. In women with BOT recurrence in a single ovary and in women with bilateralovarian involvement when the conservative management is not possible, other fertility preservation strategiesare available, but still experimental.ObjectifsLes tumeurs frontières de l’ovaire (TFO) représentent 10 à 20 % des tumeurs séreuses de l’ovaire et surviennentdans près d’un tiers des cas chez des femmes âgées de moins de 40 ans, n’ayant pas toujours accomplileur projet conceptionnel. Ainsi, la problématique de la fertilité dans la prise en charge des TFO doit être miseau premier plan.MéthodesUne sélection bibliographique a été réalisée dans PubMed de 1988 à mai 2019 inclus, sur les thématiques :infertilité et TFO, préservation de la fertilité et TFO.Résultats et conclusionsIl est recommandé de proposer une consultation spécialisée de Médecine de la reproduction lors du diagnosticde TFO chez une patiente en âge de procréer. Il est recommandé de délivrer une information complèteaux patientes, sur le risque de baisse de réserve ovarienne faisant suite à un traitement chirurgical de TFO. Ilest recommandé de s’appuyer sur les scores d’évaluation du risque de récidive, l’étude des paramètres d’infertilitéet de réserve ovarienne pour délivrer une information complète quant au risque d’infertilité des patientesprésentant une TFO (grade C). Lorsqu’elle est possible, une stratégie chirurgicale conservatrice est recommandéepour préserver la fertilité des femmes en âge de procréer en cas de TFO (grade C). Après traitementoptimal d’une TFO, il n’existe pas dans la littérature de donnée contre-indiquant formellement le recours àune stimulation ovarienne. Néanmoins, en cas de facteurs pronostics histologiques péjoratifs (implants), lerecours à une stimulation ovarienne sera discuté au cas par cas dans le cadre d’une RCP. En cas d’infertilitéaprès traitement conservateur d’une TFO, il n’existe pas de données justifiant un délai entre le traitementchirurgical et la prise en charge en assistance médicale à la procréation. La stimulation ovarienne dans le cadred’une AMP chez les femmes ayant été traitées de façon conservatrice pour TFO ne semble pas augmenter lerisque de récidive (grade C). En cas de traitement conservateur (chirurgie complète et stadification), il n’existepas de contre-indication dans la littérature à réaliser une stimulation ovarienne en vue d’une vitrificationovocytaire pour préservation de fertilité (PF). En présence de critères histologiques péjoratifs (implants), lapossibilité d’une stimulation ovarienne sera à discuter au cas par cas en RCP avant PF. Pour les femmes dontle traitement chirurgical ne peut être conservateur sur les annexes ou pour les patientes présentant une récidivede TFO sur ovaire unique, plusieurs techniques de préservation de la fertilité sont décrites dans la littératuremais avec des niveaux de preuves insuffisants pour pouvoir les recommander

Stimulation Duration in Patients with Early Oocyte Maturation Triggering Criteria Does Not Impact IVF-ICSI Outcomes

Results from studies reporting the optimal stimulation duration of IVF-ICSI cycles are inconsistent. The aim of this study was to determine whether, in the presence of early ovulation-triggering criteria, prolonged ovarian stimulation modified the chances of a live birth. This cross-sectional study included 312 women presenting triggering criteria beginning from D8 of ovarian stimulation. Among the 312 women included in the study, 135 were triggered for ovulation before D9 (D ≤ nine group) and 177 after D9 (D > nine group). The issues of fresh +/− frozen embryo transfers were taken into consideration. Cumulative clinical pregnancy and live-birth rates after fresh +/− frozen embryo transfers were similar in both groups (37% versus 46.9%, p = 0.10 and 19.3% versus 28.2%, p = 0.09, respectively). No patient characteristics were found to be predictive of a live birth depending on the day of ovulation trigger. Postponing of ovulation trigger did not impact pregnancy or live-birth rates in early responders. A patient’s clinical characteristics should not influence the decision process of ovulation trigger day in early responders. Further prospective studies should be conducted to support these findings

Impact of blood hypercoagulability on in vitro fertilization outcomes: a prospective longitudinal observational study

Abstract Background Blood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome. Methods Thirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included. In the IVF-group, blood was collected at baseline, 5–8 days after administration of gonadotropin-releasing hormone agonist (GnRH), before and two weeks after administration of human follicular stimulating hormone (FSH). Pregnancy was monitored by measurement of βHCG performed 15 days after embryo transfer. Thrombin generation (TG), minimal tissue factor-triggered whole blood thromboelastometry (ROTEM®), procoagulant phospholipid clotting time (Procoag-PPL®), thrombomodulin (TMa), tissue factor activity (TFa), factor VIII (FVIII), factor von Willebrand (FvW), D-Dimers and fibrinogen were assessed at each time point. Results Positive IVF occurred in 15 women (40%). At baseline, the IVF-group showed significantly increased TG, TFa and TMa and significantly shorter Procoag-PPL versus the control group. After initiation of hormone treatment TG was significantly higher in the IVF-positive as compared to the IVF-negative group. At all studied points, the Procoag-PPL was significantly shorter and the levels of TFa were significantly higher in the IVF-negative group compared to the IVF-positive one. The D-Dimers were higher in the IVF negative as compared to IVF positive group. Multivariate analysis retained the Procoag-PPL and TG as predictors for the IVF outcome. Conclusions Diagnosis of women with hypercoagulability and their stratification to risk of IVF failure using a model based on the Procoag-PPL and TG is a feasible strategy for the optimization of IVF efficiency that needs to be validated in prospective trials

Outcomes of fertility preservation in women with endometriosis: comparison of progestin-primed ovarian stimulation versus antagonist protocols

Abstract Background PPOS protocols, initially described for FP in women with cancer, have many advantages compared to antagonist protocols. PPOS protocols were not evaluated for women with endometriosis. The objective of the study was to describe fertility preservation outcomes in women with endometriosis and to compare an antagonist protocol with a Progestin-Primed Ovarian Stimulation (PPOS) protocol. Method We conducted a prospective cohort study associated with a cost-effectiveness analysis in a tertiary-care university hospital. The measured outcomes included the numbers of retrieved and vitrified oocytes, and direct medical costs. In the whole population, unique and multiple linear regressions analysis were performed to search for a correlation between individual characteristics and the number of retrieved oocyte. Results We included 108 women with endometriosis who had a single stimulation cycle performed with either an antagonist or a PPOS protocol. Overall, 8.1 ± 6.6 oocytes were retrieved and 6.4 ± 5.6 oocytes vitrified per patient. In the multiple regression model, age (p = 0.001), prior ovarian surgery (p = 0.035), and anti-Mullerian hormone level (p = 0.001) were associated with the number of retrieved oocytes. Fifty-four women were stimulated with an antagonist protocol, and 54 with a PPOS protocol. A mean of 7.9 ± 7.4 oocytes were retrieved in the antagonist group and 8.2 ± 5.6 in the PPOS group (p = 0.78). A mean of 6.4 ± 6.4 oocytes were vitrified in the antagonist group and 6.4 ± 4.7 in the PPOS group (p = 1). In the cost-effectiveness analysis, the PPOS protocol was strongly dominant over the antagonist protocol. Conclusion Fertility preservation procedures are feasible and effective for patients affected by endometriosis. Antagonist and PPOS protocols were associated with similar results but the medico-economic analysis was in favor of PPOS protocols

New Anti-Müllerian Hormone Target Genes Involved in Granulosa Cell Survival in Women With Polycystic Ovary Syndrome

International audiencePurpose : A protective effect of anti-Müllerian hormone (AMH) on follicle atresia was recently demonstrated using long-term treatments, but this effect has never been supported by mechanistic studies. This work aimed to gain an insight into the mechanism of action of AMH on follicle atresia and on how this could account for the increased follicle pool observed in women with polycystic ovary syndrome (PCOS).Methods : In vivo and in vitro experiments were performed to study the effects of AMH on follicle atresia and on the proliferation and apoptosis of granulosa cells (GCs). RNA-sequencing was carried out to identify new AMH target genes in GCs. The expression of some of these genes in GCs from control and PCOS women was compared using microfluidic real time quantitative RT-PCR.Results : A short-term AMH treatment prevented follicle atresia in prepubertal mice. Consistent with this result, AMH inhibited apoptosis and promoted proliferation of different models of GCs. Moreover, integrative biology analyses of 965 AMH target genes identified in 1 of these GC models, confirmed that AMH had initiated a gene expression program favoring cell survival and proliferation. Finally, on 43 genes selected among the most up- and down-regulated AMH targets, 8 were up-regulated in GCs isolated from PCOS women, of which 5 are involved in cell survival.Main conclusions : Our results provide for the first time cellular and molecular evidence that AMH protects follicles from atresia by controlling GC survival and suggest that AMH could participate in the increased follicle pool of PCOS patients

Predicting the likelihood of a live birth for women with endometriosis-related infertility

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Oocyte Vitrification for Fertility Preservation in Women with Benign Gynecologic Disease: French Clinical Practice Guidelines Developed by a Modified Delphi Consensus Process

International audienceInternational guidelines are published to provide standardized information and fertility preservation (FP) care for adults and children. The purpose of the study was to conduct a modified Delphi process for generating FP guidelines for BGD. A steering committee identified 42 potential FP practices for BGD. Then 114 key stakeholders were asked to participate in a modified Delphi process via two online survey rounds and a final meeting. Consensus was reached for 28 items. Among them, stakeholders rated age-specific information concerning the risk of diminished ovarian reserve after surgery as important but rejected proposals setting various upper and lower age limits for FP.All women should be informed about the benefit/risk balance of oocyte vitrification—in particular about the likelihood of live birth according to age. FP should not be offered in rASRM stages I and II endometriosis without endometriomas. These guidelines could be useful for gynecologists to identify situations at risk of infertility and to better inform women with BGDs who might need personalizedcounseling for FP

Management of endometriosis CNGOF/HAS clinical practice guidelines

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