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.

[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.

[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.

[Oncofertility program at the Montpellier university hospital 2 years after]. / Programme de préservation de la fertilité féminine au CHRU de Montpellier 2ans après.

OBJECTIVE: Female fertility preservation in the context of cancer management is crucial for patient's health care. The aim of this study was to evaluate the oncofertility practice at our university hospital of Montpellier since 2011. PATIENTS AND METHODS: The evaluation of management of young patients referred to Montpellier University Hospital from September 2011 to September 2013 for oncofertility counselling before cancer treatment. RESULTS: Seventy-one patients were referred to a specialized oncofertility center. Forty-two patients (59.1%) were included in the oncofertility program. Twenty-two patients (31%) were proposed for oocyte vitrification after COS protocol, eight patients (11.3%) for ovarian tissue cryoconservation, seven patients (9.9%) for GnRH injections, three patients (4.2%) ovarian transposition and two patients (2.8%) for embryo cryopreservation. Among the 42 indications of fertility preservation, only 18 will have finally taken place. CONCLUSION: Oncofertility counselling for young patients should now be part of the cancer management. It involves multidisciplinary teams. Further information of both oncologists and patients is needed to improve this new approach in the field of cancer treatments.

[Effects of artificial shrinkage prior to vitrification in a closed system: a randomized controlled trial]. / Effets de la réduction artificielle du blastocèle avant vitrification en système fermé : étude contrôlée randomisée.

OBJECTIVE: To evaluate the effect of induced blastocoele shrinkage before vitrification in a closed carrier device. PATIENTS AND METHODS: Prior to vitrification, blastocyst cavity was artificially shrinked by laser pulse or not treated according to a 2:1 randomized procedure. A total of 185 warming cycles from April 2011 to March 2013 have been analyzed. Clinical pregnancy rate and survival rate were compared between the two groups. The mean (±SD) women age was 33.5±5.7 years for both groups. RESULTS: The pregnancy rate in the group with artificial reduction of the cavity was higher ([32/67] 47.7%) than in the control group but not significantly ([43/113] 38%). The survival rate in the artificial shrinkage group was significantly higher compared with the control group : 99% (102/103) and 91.8% (168/183) respectively (P=0.01). DISCUSSION AND CONCLUSION: This study reveals that artificial shrinkage of blastocoelic cavity by laser pulse before vitrification in a closed carrier device improves survival rate after warming.

Emergency IVF for embryo freezing to preserve female fertility: a French multicentre cohort study.

STUDY QUESTION: What are the outcomes of French emergency IVF procedures involving embryo freezing for fertility preservation before gonadotoxic treatment? SUMMARY ANSWER: Pregnancy rates after emergency IVF, cryopreservation of embryos, storage, thawing and embryo transfer (embryo transfer), in the specific context of the preservation of female fertility, seem to be similar to those reported for infertile couples undergoing ART. STUDY DESIGN, SIZE, DURATION: A French retrospective multicentre cohort study initiated by the GRECOT network-the French Study Group for Ovarian and Testicular Cryopreservation. We sent an e-mail survey to the 97 French centres performing the assisted reproduction technique in 2011, asking whether the centre performed emergency IVF and requesting information about the patients' characteristics, indications, IVF cycles and laboratory and follow-up data. The response rate was 53.6% (52/97). PARTICIPANTS/MATERIALS, SETTING, METHODS: Fourteen French centres reported that they performed emergency IVF (56 cycles in total) before gonadotoxic treatment, between 1999 and July 2011, in 52 patients. MAIN RESULTS AND THE ROLE OF CHANCE: The patients had a mean age of 28.9 ± 4.3 years, and a median length of relationship of 3 years (1 month-15 years). Emergency IVF was indicated for haematological cancer (42%), brain tumour (23%), sarcoma (3.8%), mesothelioma (n = 1) and bowel cancer (n = 1). Gynaecological problems accounted for 17% of indications. In 7.7% of cases, emergency IVF was performed for autoimmune diseases. Among the 52 patients concerned, 28% (n = 14) had undergone previous courses of chemotherapy before beginning controlled ovarian stimulation (COS). The initiation of gonadotoxic treatment had to be delayed in 34% of the patients (n = 19). In total, 56 cycles were initiated. The mean duration of stimulation was 11.2 ± 2.5 days, with a mean peak estradiol concentration on the day on which ovulation was triggered of 1640 ± 1028 pg/ml. Three cycles were cancelled due to ovarian hyperstimulation syndrome (n = 1), poor response (n = 1) and treatment error (n = 1). A mean of 8.2 ± 4.8 oocytes were retrieved, with 6.1 ± 4.2 mature oocytes and 4.4 ± 3.3 pronuclear-stage embryos per cycle. The mean number of embryos frozen per cycle was 4.2 ± 3.1. During follow-up, three patients died from the consequences of their disease. For the 49 surviving patients, 22.5% of the couples concerned (n = 11) requested embryo replacement. A total of 33 embryos were thawed with a post-thawing survival rate of 76%. Embryo replacement was finally performed for 10 couples with a total of 25 embryos transferred, leading to one biochemical pregnancy, one miscarriage and three live births. Clinical pregnancy rate and live birth per couple who wanted a pregnancy after cancer were, respectively, 36% (95% CI = 10.9-69.2%) and 27% (95% CI = 6.0-61%). LIMITATIONS, REASONS FOR CAUTION: The overall response rate for clinics was 53.6%. Therefore, it is not only that patients may not have been included, but also that those that were included were biased towards the University sector with a response rate of 83% (25/30) for a small number of patients. WIDER IMPLICATIONS OF THE FINDINGS: According to literature, malignant disease is a risk factor for a poor response to COS. However, patients having emergency IVF before gonadotoxic treatment have a reasonable chance of pregnancy after embryo replacement. Embryo freezing is a valuable approach that should be included among the strategies used to preserve fertility. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study. None of the authors has any conflict of interest to declare.

[Low circulating anti-Müllerian hormone and normal follicle stimulating hormone levels: which prognosis in an IVF program?]. / Pronostic en fécondation in vitro des patientes ayant une AMH basse et une FSH normale.

OBJECTIVE: To evaluate the results of controlled ovarian hyperstimulation (COH) for IVF in patients with low anti-Müllerian hormone (AMH) and normal basal follicle stimulating hormone (FSH) and Estradiol levels (≤50 pg/mL). PATIENTS AND METHODS: A retrospective cohort study including 704 patients for whom AMH and FSH levels (measured between days 3 and 5 of the menstrual cycle) were available, is performed in the IVF center at the Sèvres Hospital (France). Three groups are designed and analyzed: group 1 with AMH less or equal to 2 ng/mL and FSH less or equal to 10 mUI/mL (study group), Group 2 with AMH greater than 2 ng/mL and FSH less or equal to 10 mUI/mL (control group) and Group 3 with AMH less or equal to 2 ng/mL and FSH greater than 10 mUI/mL (group with decreased ovarian reserve). RESULTS: IVF outcome for patients from the study group is significantly worse than that of the second but not than that of the third group. In the first group, the number of retrieved oocytes, the number of total obtained embryos, the clinical pregnancy rate and the live birth rate are significantly lower than in the second group; moreover, there are more cancelled cycles because of poor response in the first group. There is no difference with the third group. DISCUSSION AND CONCLUSIONS: This study shows that women with a low baseline AMH have a similar response to COH to the poor responders patients with a decreased ovarian reserve revealed by an elevated FSH level. Thus, when a woman undergoing IVF cycle presents a low AMH, she might be considered as a poor responder patient regardless of the FSH level and, although the clinical pregnancy rate is not so disappointing (18%), the couple should be informed of a higher risk of cycle cancellation.

[Septo-optic dysplasia (De Morsier's syndrome). About one case discovered during the pregnancy]. / Découverte anténatale d'une dysplasie septo-optique (syndrome de De Morsier).

The authors report a case of septo-optic dysplasia discovered during the pregnancy without another abnormality. It's a rare cerebral abnormality that is characterized by an absence of septum pellucidum associated to a hypoplasia of ways and optic chiasm to variable degrees. Discovery is often made for adulthood. Future is extremely wide. It is determined with the arisen to different degrees of incapacity of Pituitary gland, psychomotor delay of variable intensity with mental deficiency, a visual confusion, and a confusion of the regulation of the temperature.

[Preservation of fertility in case of sterilizing treatment]. / Préservation de la fertilité en cas de traitement stérilisant.

The different options of fertility preservation must be approached with all patients before initiating any cancer therapy and physicians should refer each patient treated during their reproductive years to specialists in a specialized center that will evaluate the best available alternatives to preserve male and female fertility.The only efficiently proven ways of fertility preservation are sperm cryopreservation for men and embryo cryopreservation to preserve couple fertility. However, the recent progress observed with oocyte cryopreservation (in particular the oocyte vitrification) may change our practices in the future if vitrification is allowed in France. Although the law of Bioethics of 2004 authorizes the ovarian cryopreservation today, its modalities of use stay at present at the stage of the research. But in spite of the low number of published births today in France and in the world, the ovarian tissue cryopreservation is a promising technique. It remains the last possible alternative to protect fertility of prepubertal girls. The sperm cryopreservation must be systematically proposed to all men (even teenagers) undergoing a treatment for cancer potentially harmful for their fertility whatever their sperm quality. The testicular tissue cryopreservation is also a method to be discussed for adults, teenagers in case of failure of sperm banking or for prepubertal boys.

[In Vitro Fertilization: beware of oocyte retrieval without oocyte!]. / Fécondation in vitro : ponction blanche : méfions-nous !

A 30-year-old woman undergoing an In Vitro Fertilization (IVF) treatment for tubal infertility and for whom no oocyte was retrieved at the puncture ("white puncture") presented an ectopic pregnancy. The patient was asymptomatic except some bleeding events reported for several days prior to the puncture. The ovulation monitoring was normal throughout the stimulation by gonadotrophin and hCG was administered for the final oocyte maturation on the twelfth day of stimulation at a rate of 2771 pg/ml of estradiol with a perfect ultrasound follicular growth. This case demonstrates that we have to beware of a "white puncture" and that the hCG measurement the day of the oocyte retrieval is necessary because of the possibility of an ectopic pregnancy.

[Hypothyroidism: from the desire for pregnancy to delivery]. / Hypothyroïdie: du désir de grossesse à l'accouchement.

The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well.