The BISTIM study: a randomized controlled trial comparing dual ovarian stimulation (duostim) with two conventional ovarian stimulations in poor ovarian responders undergoing IVF.

STUDY QUESTION: Is the total number of oocytes retrieved with dual ovarian stimulation in the same cycle (duostim) higher than with two consecutive antagonist cycles in poor responders? SUMMARY ANSWER: Based on the number of total and mature oocytes retrieved in women with poor ovarian response (POR), there is no benefit of duostim versus two consecutive antagonist cycles. WHAT IS KNOWN ALREADY: Recent studies have shown the ability to obtain oocytes with equivalent quality from the follicular and the luteal phase, and a higher number of oocytes within one cycle when using duostim. If during follicular stimulation smaller follicles are sensitized and recruited, this may increase the number of follicles selected in the consecutive luteal phase stimulation, as shown in non-randomized controlled trials (RCT). This could be particularly relevant for women with POR. STUDY DESIGN, SIZE, DURATION: This is a multicentre, open-labelled RCT, performed in four IVF centres from September 2018 to March 2021. The primary outcome was the number of oocytes retrieved over the two cycles. The primary objective was to demonstrate in women with POR that two ovarian stimulations within the same cycle (first in the follicular phase, followed by a second in the luteal phase) led to the retrieval of 1.5 (2) more oocytes than the cumulative number of oocytes from two consecutive conventional stimulations with an antagonist protocol. In a superiority hypothesis, with power 0.8 alpha-risk 0.05 and a 35% cancellation rate, 44 patients were needed in each group. Patients were randomized by computer allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eighty-eight women with POR, defined using adjusted Bologna criteria (antral follicle count ≤5 and/or anti-Müllerian hormone ≤1.2 ng/ml) were randomized, 44 in the duostim group and 44 in the conventional (control) group. HMG 300 IU/day with flexible antagonist protocol was used for ovarian stimulation, except in luteal phase stimulation of the duostim group. In the duostim group, oocytes were pooled and inseminated after the second retrieval, with a freeze-all protocol. Fresh transfers were performed in the control group, frozen embryo transfers were performed in both control and duostim groups in natural cycles. Data underwent intention-to-treat and per-protocol analyses. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference between the groups regarding demographics, ovarian reserve markers, and stimulation parameters. The mean (SD) cumulative number of oocytes retrieved from two ovarian stimulations was not statistically different between the control and duostim groups, respectively, 4.6 (3.4) and 5.0 (3.4) [mean difference (MD) [95% CI] +0.4 [-1.1; 1.9], P = 0.56]. The mean cumulative numbersof mature oocytes and total embryos obtained were not significantly different between groups. The total number of embryos transferred by patient was significantly higher in the control group 1.5 (1.1) versus the duostim group 0.9 (1.1) (P = 0.03). After two cumulative cycles, 78% of women in the control group and 53.8% in the duostim group had at least one embryo transfer (P = 0.02). There was no statistical difference in the mean number of total and mature oocytes retrieved per cycle comparing Cycle 1 versus Cycle 2, both in control and duostim groups. The time to the second oocyte retrieval was significantly longer in controls, at 2.8 (1.3) months compared to 0.3 (0.5) months in the duostim group (P < 0.001). The implantation rate was similar between groups. The cumulative live birth rate was not statistically different, comparing controls versus the duostim group, 34.1% versus 17.9%, respectively (P = 0.08). The time to transfer resulting in an ongoing pregnancy did not differ in controls 1.7 (1.5) months versus the duostim group, 3.0 (1.6) (P = 0.08). No serious adverse events were reported. LIMITATIONS, REASONS FOR CAUTION: The RCT was impacted by the coronavirus disease 2019 pandemic and the halt in IVF activities for 10 weeks. Delays were recalculated to exclude this period; however, one woman in the duostim group could not have the luteal stimulation. We also faced unexpected good ovarian responses and pregnancies after the first oocyte retrieval in both groups, with a higher incidence in the control group. However, our hypothesis was based on 1.5 more oocytes in the luteal than the follicular phase in the duostim group, and the number of patients to treat was reached in this group (N = 28). This study was only powered for cumulative number of oocytes retrieved. WIDER IMPLICATIONS OF THE FINDINGS: This is the first RCT comparing the outcome of two consecutive cycles, either in the same menstrual cycle or in two consecutive menstrual cycles. In routine practice, the benefit of duostim in patients with POR regarding fresh embryo transfer is not confirmed in this RCT: first, because this study demonstrates no improvement in the number of oocytes retrieved in the luteal phase after follicular phase stimulation, in contrast to previous non-randomized studies, and second, because the freeze-all strategy avoids a pregnancy with fresh embryo transfer after the first cycle. However, duostim appears to be safe for women. In duostim, the two consecutive processes of freezing/thawing are mandatory and increase the risk of wastage of oocytes/embryos. The only benefit of duostim is to shorten the time to a second retrieval by 2 weeks if accumulation of oocytes/embryos is needed. STUDY FUNDING/COMPETING INTERESTS: This is an investigator-initiated study supported by a research Grant from IBSA Pharma. N.M. declares grants paid to their institution from MSD (Organon France); consulting fees from MSD (Organon France), Ferring, and Merck KGaA; honoraria from Merck KGaA, General Electrics, Genevrier (IBSA Pharma), and Theramex; support for travel and meetings from Theramex, Merck KGaG, and Gedeon Richter; and equipment paid to their institution from Goodlife Pharma. I.A. declares honoraria from GISKIT and support for travel and meetings from GISKIT. G.P.-B. declares Consulting fees from Ferring and Merck KGaA; honoraria from Theramex, Gedeon Richter, and Ferring; payment for expert testimony from Ferring, Merck KGaA, and Gedeon Richter; and support for travel and meetings from Ferring, Theramex, and Gedeon Richter. N.C. declares grants from IBSA pharma, Merck KGaA, Ferring, and Gedeon Richter; support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Gedeon Richter, and Theramex; and participation on advisory board from Merck KGaA. E.D. declares support for travel and meetings from IBSA pharma, Merck KGaG, MSD (Organon France), Ferring, Gedeon Richter, Theramex, and General Electrics. C.P.-V. declares support for travel and meetings from IBSA Pharma, Merck KGaA, Ferring, Gedeon Richter, and Theramex. M.Pi. declares support for travel and meetings from Ferring, Gedeon Richetr, and Merck KGaA. M.Pa. declares honoraria from Merck KGaA, Theramex, and Gedeon Richter; support for travel and meetings from Merck KGaA, IBSA Pharma, Theramex, Ferring, Gedeon Richter, and MSD (Organon France). H.B.-G. declares honoraria from Merck KGaA, and Gedeon Richter and support for travel and meetings from Ferring, Merck KGaA, IBSA Pharma, MSD (Organon France), Theramex, and Gedeon Richter. S.G. and M.B. have nothing to declare. TRIAL REGISTRATION NUMBER: Registration number EudraCT: 2017-003223-30. ClinicalTrials.gov identifier: NCT03803228. TRIAL REGISTRATION DATE: EudraCT: 28 July 2017. ClinicalTrials.gov: 14 January 2019. DATE OF FIRST PATIENT'S ENROLMENT: 3 September 2018.

[Is there a curative treatment for oligometastases? Lung radiofrequency ablation]. / Oligométastases : prise en charge thérapeutique à visée curative ? Radiofréquence pulmonaire.

Percutaneous ablation allows to treat tumours with temperature modifications. These non-invasive techniques are useful to treat metastatic lung tumours in patients with a slowly evolving disease, which requires multiple local treatment. Ablation is therefore proposed as a locoregional treatment because it has a minimal impact on the lung. Other advantages are its efficacy and a low morbidity. Limits may be the tumour size and its location.

Radiofrequency ablation of bone tumours.

The indications for radiofrequency bone ablation in the case of benign tumours (osteoid osteoma, osteoblastoma) are curative, whereas for bone metastases, the prime aim is palliative analgesia. The failure rate for osteoid osteomas is low (<15%), and 70 to 90% of patients with metastases experience considerable relief, but if the treatment fails, it can be offered again. In the spine, heating can damage neighboring nerve structures, which means they need to be protected (CO(2) dissection). Radiofrequency ablation may be combined with an injection of cement. The osteonecrosis resulting from heating is painful and justifies performing the procedure under general anesthesia.

[Fluoroscopy-guided percutaneous biopsies: value of real-time guidance with image fusion software]. / Biopsies percutanées sous scopie: apport d'un logiciel de guidage en temps réel avec images fusionnées.

Based on our preliminary experience with fluoroscopy-guided biopsy using a real-time 3D image fusion software, several biopsies may be performed in the interventional radiology suite as opposed to under CT guidance: percutaneous lung and bone biopsies are easily performed for lesions larger than 15 mm.

Sarcoma lung metastases treated with percutaneous radiofrequency ablation: results from 29 patients.

PURPOSE: We aimed to determine safety and efficacy of radiofrequency ablation (RFA) in the treatment of lung metastases arising from sarcoma. METHODS: Between 2002 and 2009, 29 patients (mean age 51 years) treated for metastatic sarcoma with a maximum of 5 lung metastases treatable with RFA were followed prospectively. The end points were local efficacy (assessed by computed tomography during the follow-up period), complications, and survival (overall and disease-free). RESULTS: A total of 47 metastases were treated with RFA. Median follow-up time was 50 months (range 28-72 months). Pneumothorax was the most frequent complication and occurred in 68.7% of the procedures. The 1- and 3-year survival rates were 92.2% (95% confidence interval [CI] 0.73-0.98) and 65.2% (95% CI 0.42-0.81), respectively. Disease-free survival was 7 months (95% CI 3.5-10). Five recurrences on RFA sites were noted during follow-up. CONCLUSIONS: RFA is safe and efficient in the treatment of lung metastasis originating from sarcomas. RFA may provide a low-morbidity alternative to surgery, being less invasive and preserving the patient's ability to undergo possible repeat operations.

[Radiofrequency ablation in the treatment of liver and lung tumors]. / Traitement par radiofréquence des tumeurs hépatiques et pulmonaires.

Radiofrequency (RF) ablation is a technique of thermotherapy which emerged over the last fifteen years in the field of oncology. RF directed toward a specific tumor mass is known to be very effective (over 90%) for treating tumors less than 2.5 cm. RF is used for patients with early-stage lung or liver cancers who are not surgical candidates, With improvements in systemic therapy, increasing interest in the use of local therapy for metastases has arisen. Eradication of residual metastases via local therapies has a sense in patients with stabilized disease. Nonsurgical alternative like RF has become popular because it is less invasive than surgery and has demonstrated great efficiency. Nevertheless prospective randomized trials to compare RF with surgery are difficult to achieve, prospective studies are needed to better evaluate the technique.

[Methods and efficacy of medical and surgical treatment of non functional menorrhagia]. / Modalités et efficacité des traitements médicaux et chirurgicaux devant des ménométrorragies organiques.

OBJECTIVES: To assess the efficacy of therapies in menorrhagia related to atypical endometrial hyperplasia, polyps, myoma, adenomyosis and arteriovenous malformation of the uterus. MATERIALS AND METHODS: Medline and Cochrane contents were searched to June 2008. RESULTS: Atypical endometrial hyperplasia is classically treated by hysterectomy, but may temporarily regress under hormone therapy (progestins, Gn-RH agonists) in women of childbearing age. Hysteroscopic resection is the standard treatment for endometrial polyps. Recurrence of bleeding is reduced by combining it with endometrial ablation. Myoma-related menorrhagia can be treated by Gn-RH agonists for 3 months or levonorgestrel in utero (LNG-IUS). Hysteroscopic resection is the standard treatment of submucous myomas. Interstitial myomas can be treated by myomectomy, myolysis, uterine artery embolisation or occlusion, or hysterectomy. Laparoscopic myomectomy and uterine artery embolisation are effective, well tolerated, and the best researched. LNG-IUS is effective and well tolerated to treat adenomyosis-related menorrhagia. The effect of other conservative treatments of the uterus (endometrial ablation, uterine artery embolisation or occlusion) is limited, especially in case of deep and extensive adenomyosis. Uterine artery embolisation is the standard treatment for arteriovenous malformation. CONCLUSIONS: Numerous medical and technical innovations have been recently developed as conservative treatments for menorrhagia. However, hysterectomy remains the standard treatment of atypical endometrial hyperplasia and adenomyosis.

[Endometrial hyperplasia: A review]. / Les hyperplasies de l'endomètre.

Endometrial hyperplasias can be divided into two categories based on the presence or absence of cytological atypia and further classified as simple or complex according to the extent of architectural abnormalities. They are usually diagnosed because of irregular bleeding in perimenopause. Hysteroscopy with a biopsy gives a more accurate diagnosis than transvaginal ultrasonography, sonohysterography, or blind curettage. Endometrial hyperplasias with no cytological atypia, regarded as a response to unopposed endogenous estrogenic stimulation, are normally treated with progestins. The intra-uterine route (levonorgestrel intra-uterine system) is more effective and better tolerated than the oral route. Either conservative surgery (endometrial resection, thermal ablation) or radical surgery (hysterectomy) in the case of other genital diseases is performed on women who did not respond to medical treatment. Endometrial hyperplasias with cytological atypia, considered as intra-epithelial neoplasias, are traditionally treated by hysterectomy. The absence of management protocols in the literature offers various treatment options and indications. Gonadotropin-releasing hormone agonists, danazol, or aromatase inhibitor are effective, but have adverse effects and are expensive. Endometrial ablation can be performed as a first line therapy in women suffering from bleeding related to hyperplasia without cytological atypia. Medical treatment may be offered to young women suffered from hyperplasias with cytological atypia and desiring pregnancy.

MR imaging of myocardial haematoma after blunt chest injury.

Myocardial contusion after a chest trauma is a frequently under-diagnosed injury. We report two cases of myocardial contusion in which MR imaging, thanks to its contrast capability, was able to assess the presence of a haematoma and in one case to demonstrate the recovery of the lesion.