Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome? A multicenter study and systematic review of the literature.

STUDY QUESTION: Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome (TS)? SUMMARY ANSWER: The oocyte cryopreservation strategy is not well adapted for all TS women as their combination of high basal FSH with low basal AMH and low percentage of 46,XX cells in the karyotype significantly reduces the chances of freezing sufficient mature oocytes for fertility preservation. WHAT IS KNOWN ALREADY: An oocyte cryopreservation strategy requiring numerous stimulation cycles is needed to preserve fertility in TS women, to compensate for the low ovarian response, the possible oocyte genetic alterations, the reduced endometrial receptivity, and the increased rate of miscarriage, observed in this specific population. The validation of reliable predictive biomarkers of ovarian response to hormonal stimulation in TS patients is necessary to help practitioners and patients choose the best-personalized fertility preservation strategy. STUDY DESIGN, SIZE, DURATION: A retrospective bicentric study was performed from 1 January 2011 to 1 January 2023. Clinical and biological data from all TS women who have received from ovarian stimulation for fertility preservation were collected. A systematic review of the current literature on oocyte retrieval outcomes after ovarian stimulation in TS women was also performed (PROSPERO registration number: CRD42022362352). PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 14 TS women who had undergone ovarian stimulation for fertility preservation were included, representing the largest cohort of TS patients published to date (n = 14 patients, 24 cycles). The systematic review of the literature identified 34 additional TS patients with 47 oocyte retrieval outcomes after ovarian stimulation in 14 publications (n = 48 patients, n = 71 cycles in total). MAIN RESULTS AND THE ROLE OF CHANCE: The number of cryopreserved mature oocytes on the first cycle for TS patients was low (4.0 ± 3.7). Oocyte accumulation was systematically proposed to increase fertility potential and was accepted by 50% (7/14) of patients (2.4 ± 0.5 cycles), leading to an improved total number of 10.9 ± 7.2 cryopreserved mature oocytes per patient. In the group who refused the oocyte accumulation strategy, only one patient exceeded the threshold of 10 mature cryopreserved oocytes. In contrast, 57.1% (4/7) and 42.9% (3/7) of patients who have underwent the oocyte accumulation strategy reached the threshold of 10 and 15 mature cryopreserved oocytes, respectively (OR = 8 (0.6; 107.0), P = 0.12; OR= 11 (0.5; 282.1), P = 0.13). By analyzing all the data published to date and combining it with our data (n = 48 patients, n = 71 cycles), low basal FSH and high AMH concentrations as well as a higher percentage of 46,XX cells in the karyotype were significantly associated with a higher number of cryopreserved oocytes after the first cycle. Moreover, the combination of low basal FSH concentration (<5.9 IU/l), high AMH concentration (>1.13 ng/ml), and the presence of 46,XX cells (>1%) was significantly predictive of obtaining at least six cryopreserved oocytes in the first cycle, representing objective criteria for identifying patients with real chances of preserving an adequate fertility potential by oocyte cryopreservation. LIMITATIONS, REASONS FOR CAUTION: Our results should be analyzed with caution, as the optimal oocyte number needed for successful live birth in TS patients is still unknown due to the low number of reports their oocyte use in the literature to date. WIDER IMPLICATIONS OF THE FINDINGS: TS patients should benefit from relevant clinical evaluation, genetic counseling and psychological support to make an informed choice regarding their fertility preservation technique, as numerous stimulation cycles would be necessary to preserve a high number of oocytes. STUDY FUNDING/COMPETING INTEREST(S): This research received no external funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Usability, accuracy, and cost-effectiveness of a medical software for early pregnancies: a retrospective study.

STUDY QUESTION: Can early pregnancies be accurately and cost-effectively diagnosed and managed using a new medical computerized tool? SUMMARY ANSWER: Compared to the standard clinical approach, retrospective implementation of the new medical software in a gynaecological emergency unit was correlated with more accurate diagnosis and more cost-effective management. WHAT IS KNOWN ALREADY: Early pregnancy complications are responsible for a large percentage of consultations, mostly in emergency units, with guidelines becoming complex and poorly known/misunderstood by practitioners. STUDY DESIGN, SIZE, DURATION: A total of 780 gynaecological emergency consultations (446 patients), recorded between November 2018 and June 2019 in a tertiary university hospital, were retrospectively encoded in a new medical computerized tool. The inclusion criteria were a positive hCG test result, ultrasonographical visualization of gestational sac, and/or embryo corresponding to a gestational age of 14 weeks or less. Diagnosis and management suggested by the new computerized tool are named eDiagnoses, while those provided by a gynaecologist member of the emergency department staff are called medDiagnoses. PARTICIPANTS/MATERIALS, SETTING, METHODS: Usability was the primary endpoint, with accuracy and cost reduction, respectively, as secondary and tertiary endpoints. Identical eDiagnoses/medDiagnoses were considered as accurate. During follow-up visits, if the updated eDiagnoses and medDiagnoses became both identical to a previously discrepant eDiagnosis or medDiagnosis, this previous eDiagnosis or medDiagnosis was also considered as correct. Four double-blinded experts reviewed persistent discrepancies, determining the accurate diagnoses. eDiagnoses/medDiagnoses accuracies were compared using McNemar's Chi square test, sensitivity, specificity, and predictive values. MAIN RESULTS AND THE ROLE OF CHANCE: Only 1 (0.1%) from 780 registered medical records lacked data for full encoding. Out of the 779 remaining consultations, 675 eDiagnoses were identical to the medDiagnoses (86.6%) and 104 were discrepant (13.4%). From these 104, 60 reached an agreement during follow-up consultations, with 59 medDiagnoses ultimately changing into the initial eDiagnoses (98%) and only one discrepant eDiagnosis turning later into the initial medDiagnosis (2%). Finally, 24 remained discrepant at all subsequent checks and 20 were not re-evaluated. Out of these 44, the majority of experts agreed on 38 eDiagnoses (86%) and 5 medDiagnoses (11%, including four twin pregnancies whose twinness was the only discrepancy). No majority was reached for one discrepant eDiagnosis/medDiagnosis (2%). In total, the accuracy of eDiagnoses was 99.1% (675 + 59 + 38 = 772 eDiagnoses out of 779), versus 87.4% (675 + 1 + 5 = 681) for medDiagnoses (P < 0.0001). Calculating all basic costs of extra consultations, extra-medications, extra-surgeries, and extra-hospitalizations induced by incorrect medDiagnoses versus eDiagnoses, the new medical computerized tool would have saved 3623.75 Euros per month. Retrospectively, the medical computerized tool was usable in almost all the recorded cases (99.9%), globally more accurate (99.1% versus 87.4%), and for all diagnoses except twinning reports, and it was more cost-effective than the standard clinical approach. LIMITATIONS, REASONS FOR CAUTION: The retrospective study design is a limitation. Some observed improvements with the medical software could derive from the encoding by a rested and/or more experienced physician who had a better ultrasound interpretation. This software cannot replace clinical and ultrasonographical skills but may improve the compliance to published guidelines. WIDER IMPLICATIONS OF THE FINDINGS: This medical computerized tool is improving. A new version considers diagnosis and management of multiple pregnancies with their specificities (potentially multiple locations, chorioamnionicity). Prospective evaluations will be required. Further developmental steps are planned, including software incorporation into ultrasound devices and integration of previously published predictive/prognostic factors (e.g. serum progesterone, corpus luteum scoring). STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. F.B. and D.G. created the new medical software. TRIAL REGISTRATION NUMBER: NCT03993015.

[EUGIC (Extension of the Use of Gametes in Intra-Conjugal): New uses of gametes within the couple]. / EUGIC (Extension de l'Utilisation de Gamètes en IntraConjugal) : les nouveaux usages des gamètes au sein du couple.

OBJECTIVE: New possibilities for using gametes within a couple were created by the French law of August 2, 2021 related to bioethics by opening Assisted Reproductive Technics (ART) to all women. It concerns previously self-preserved gametes, thus avoiding the need for gamete donation. The objective of our study is to evaluate the perception of these new uses by ART practitioners. METHOD: A questionnaire of twelve short questions was sent to professionals concerned with gamete donation. RESULTS: One hundred and ten professionals answered the questionnaire. The majority of them approve of the Reception of Oocytes from the Partner (ROPA), notably if there is a medical indication. Requests are rarer for the care of trans* people, and raise more questions. Although less favorable to the use of eggs from trans* men, more of them support the practice when it is an alternative to oocyte donation. CONCLUSION: The acronym EUGIC (Extension of the Use of Gametes in Intra-Conjugal) makes it possible to group together these new situations generated by the change in the French law.

[Are gestational weight gain guidelines for obese women still appropriate?] / Les recommandations de prise de poids gestationnelle pour les femmes obèses sont-elles encore adaptées ?

Guidelines for adequate gestational weight gain were proposed in 2009 by the Institute of Medicine. In case of a BMI>30kg/m2, the recommended gestational weight gain should be between 5 and 9kg. However, these recommendations do not distinguish between different grades of obesity. Recent data suggest that the IOM recommendations are not restrictive enough for obese pregnant women and should be adapted to the grade of obesity.

[Assessment of genital microbiota: An emerging approach in assisted reproductive techniques]. / Évaluation du microbiote génital : une approche émergente en assistance médicale à la procréation.

The genital microbiota actively participates in women's reproductive health. Indeed, a genital dysbiosis (microbial imbalance associated with adverse effects on host health) can lead to vaginal infections (such as mycoses or bacterial vaginosis). Recent data reported that genital dysbiosis (e.g. vaginal or endometrial) was associated with fewer chances of live births in assisted reproductive technologies (ART), via decreased pregnancy rates and an increased risk of miscarriages. The presence or diversity of certain bacterial strains (in particular Gardenellavaginalis, Proteobacteria, Lactobacillusjensenii, Lactobacilluscrispatus or Atopobiumvaginae) within the genital microbiota seem to be associated with the outcomes of ART cycles, suggesting new approaches to improve ART results. In this review, we aim at presenting the state of art on the association between the female genital microbiota and ART success. The diagnostic and therapeutic approaches (i.e. probiotics, antibiotic therapy and transplantation of vaginal microbiota) in the management of patients with altered microbiota will also be discussed. The confirmation of these data in the coming years could significantly improve the management of infertile patients in ART with a more personalized approach partially based on the female genital microbiotic profile.

[Oncofertility and breast cancer at Montpellier University Hospital: Retrospective analysis of patients management since 2011]. / Oncofertilité et cancer du sein au CHRU de Montpellier : analyse rétrospective du devenir des patientes depuis 2011.

OBJECTIVE: Five to 7% of breast cancers affect women under 40 years old. The survival of these patients has been improved thanks to therapeutic advances, often to the detriment of their fertility. The objective of this study is to evaluate the activity of oncofertility and the future of young women with breast cancer managed at the Montpellier University Hospital. METHODS: This is a retrospective study including women aged from 18 to 43 years-old diagnosed with breast cancer and referred in oncofertility consultation at the Montpellier University Hospital between July 2011 and December 2018. RESULTS: 190 patients were eligible, three refused to participate to the study, hence 187 patients were included. We estimate that only 33% of young breast cancer patients potentially eligible for fertility preservation (FP) benefited from an oncofertility consultation in our region. Of these 187 patients, 58 (31%) underwent ovarian stimulation for oocyte or embryo vitrification. They were significantly younger: 32.9 vs 34.6 years old (P=0.01) and had fewer invaded lymph nodes. A total of 66 cycles were achieved and 11.4 oocytes or 3 embryos were vitrified per patient. The reuse rate was 3.6% with 91% of post cancer pregnancies being spontaneous. CONCLUSION: The oncofertility care network seems effective at the regional level. Enhancing health professionals' awareness and creating a regional register could improve our long-term follow-up.

[Comparison of birth weights of children born after slow frozen embryo replacement versus fresh embryo transfer]. / Embryons vitrifiés, embryons frais : comparaison des poids de naissance.

OBJECTIVE: It is already known that children born after slow frozen embryo replacement have a significantly higher birth weight compared to children born after fresh embryo transfer. Similar data have been reported related to frozen embryo transfer using an open vitrification system. However, few data relative to birth weight using a complete embryo closed vitrification system has been reported. The purpose of this study was to know if frozen embryo in closed vitrification system is associated with a higher birth weight compared to fresh embryo replacement. DESIGN: This was a monocentric retrospective cohort study, 371 children were issued from fresh embryo replacement and 127 from vitrified embryo transfer. MATERIALS AND METHODS: All singletons born after fresh or vitrified embryo transfer between January 2011 and April 2015 were included. Births from the vitrified or fresh transfers of egg or sperm donation, and preimplantation genetic diagnosis were excluded. In addition, pregnancies with more than one gestational sac at the first ultrasound were excluded. An analysis of covariance (ANCOVA) was used for multivariate analysis. RESULTS: Mean birth weight was 205g higher in the frozen embryo compared with fresh embryos transfer groups (3368g vs. 3163g respectively, P<0.001). This difference remained after multivariate analysis adjusted on confounding factors such as gestational age, maternal age, maternal body mass index (BMI), tobacco exposure, number of embryo transferred and birth order (P<0.001).. CONCLUSIONS: Embryo frozen in closed vitrification system is associated with a higher birth weight compared to fresh embryo replacement. Our findings are consistent with the previous studies related to slow freezing and open vitrification systems data. The effects of controlled ovarian stimulation (COS), ex vivo culture conditions and cryopreservation systems on birth weight of children born should be further explored.

[Natural cycle for frozen-thawed embryo transfer: Spontaneous ovulation or triggering by HCG]. / Transferts d'embryons congelés en cycle naturel : ovulation spontanée ou déclenchement par hCG ?

OBJECTIVE: To compare frozen-thawed embryo transfer (FET) outcomes in natural cycles according to ovulation induction: spontaneous versus recombinant human chorionic gonadotrophin (r-hCG) triggering. METHODS: This retrospective study included all patients monitored for natural cycle FET during one year. When serial monitoring were performed until spontaneous LH rise, patients were included in group A (n=38) whereas those receiving r-hCG for ovulation triggering formed group B (n=43). All embryos had been cryopreserved by a vitrification method following a previous IVF cycle. No luteal phase support had been given. We compared outcomes between the 2 groups. RESULTS: After checking groups comparability, we didn't find significant difference for the implantation rate, clinical pregnancy rate and live birth (31% vs 45%, 32% vs 51% et 21% vs 32%, respectively for group A and B). The number of monitoring was significantly lower in group B (1,9±0,8 versus 2,5±1, P=0,006). DISCUSSION: Although no consensus has been yet established, natural cycle seems indicated for normo-ovulating patients but the question of ovulation induction is still debated. In our study, triggering ovulation by r-hCG, respecting strict criteria, seems provide good results while reducing both protocol's constraints and cost.

[Poor responders: How could we improve our results?] / Mauvaises répondeuses : peut-on améliorer nos résultats ?

OBJECTIVES: Finding an efficient treatment for poor responders still poses a tremendous challenge for assisted reproductive technology. In 2011, an international consensus has been reached in Bologna on how to standardize the definition of poor ovarian response (POR) in a simple and reproducible manner. This article provides an objective assessment of the different treatment options currently available. METHODS: A search of the database PUBMED was carried out for studies published in English between October 2000 and April 2016. RESULTS: There is no ideal protocol to manage poor responders even though the antagonist protocol seems to have an advantage of clinicians. This is thanks to better patient tolerance and reduced total dose of gonadotrophin as well as shorter time of stimulation. It seems that there is no benefit in increasing the gonadotrophin daily doses over 300IU nor using any specific type of gonadotrophin. Today, there is insufficient evidence to recommend any additional treatment for poor responders. Only dehydroepiandrosterone (DHEA) seems to increase embryonic quality and pregnancy rate, however further exploration and complementary prospective studies are necessary. CONCLUSION: New treatment strategies such as "oocyte banking" or double stimulation during the same cycle, could provide new prospects in poor responders management.

[Robot-assisted laparoscopic myomectomy: comparison with abdominal myomectomy]. / La myomectomie par cœlioscopie avec assistance robotique: comparaison avec la laparotomie.

OBJECTIVE: To compare morbidity of robot-assisted laparoscopic myomectomy versus those performed by laparotomy. PATIENTS AND METHODS: It reports a monocentric retrospective case matched analysis enrolling 22 patients (six laparotomic and 16 robot-assisted laparoscopic myomectomies), needing a surgical treatment for at least one myoma oversizing 6cm. RESULTS: Both patient groups were comparable regarding their age, their weight and myoma's size. There were more complications in the laparotomy group in comparison with the robotic group (66.7%, versus 0%; P=0.002). Average intraoperative blood losses were respectively 397±377mL versus 387±349mL (P=0.71) and length of stay 7.2±0.8 days versus 3.9±2.8 days (P<0.001). None of the robot-assisted laparoscopic myomectomy needed any conversion to laparotomy. CONCLUSION: Robot-assisted laparoscopic myomectomy seems to be feasible for heavy fibroids, with a lower morbidity in comparison with laparotomy. These results must be confirmed by several wider prospective studies.