She is currently an obstetrician-gynaecologist in Montpellier and has specialized in reproductive medicine since 2015. She carried out 12-months of clinical research in reproductive medicine at the Royal Hospital for Women in Sydney in 2018 and worked on premature ovarian insufficiency and polycystic ovary syndrome.
Oocyte-secreted factors bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are critical for folliculogenesis and fertility. This study developed ELISAs for the measurement of BMP15 and GDF9 in serum and investigated their usefulness as biomarkers of female reproductive function. Serum samples were obtained from women undergoing infertility treatments (n = 154) and from perimenopausal and postmenopausal women (n = 28). Serum concentrations of BMP15 and GDF9 were analyzed in women relative to age, anti-Müllerian hormone, number of oocytes retrieved, and polycystic ovary syndrome (PCOS) after superovulation for in vitro fertilization. BMP15 and GDF9 immunoassays were validated for specificity, sensitivity (24 and 26 pg/mL, respectively), and reproducibility. BMP15 and GDF9 were detectable in 61% and 29% of women, respectively. BMP15 and GDF9 varied 64-fold and 15-fold, respectively, between women, but they did not change within subjects following ovarian stimulation with gonadotropins. Serum GDF9 concentration, but not BMP15 concentration, was associated with oocyte number retrieved in patients without PCOS (P = 0.018). GDF9 and BMP15 associations with oocyte number differed significantly (P < 0.05) with PCOS status. GDF9 concentrations were lower in poor responders (women with fewer than four oocytes retrieved or with cancelled cycles; P = 0.020). Serum BMP15, but not GDF9, was lower in women >55 years of age, compared with women of reproductive age (P < 0.01). This study develops and validates immunoassays to quantitate BMP15 and GDF9 in human serum and to correlate concentrations with female reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine.
Purpose: To assess psychological state of women who experienced postponement of ART care during the first COVID-19 wave in a French public ward of reproductive medicine. Methods: An online anonymous survey was emailed between July and August 2020 to all women whose infertility care, including the first consultation for infertility, have been delayed at the beginning of the COVID-19 pandemic. Anxiety, depression, and stress were assessed using Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS-10). Feelings about COVID-19 outbreak, lockdown and suspension of fertility care were assessed by Multiple-Choice Questions and Visual Analog Scales. Results: 435 women answered to the survey (response rate 34.6%). Mean levels of the HADS-A (anxiety), HADS-D (depression) and PSS10 were respectively 7.58(±3.85), 4.51(±3.48), and 27(±6.75). Prevalence of stress was 50.8% and almost half of women presented clear or suggestive anxiety symptoms (respectively 21.6% and 25.7%). Stress and anxiety rates were much higher than those expected in infertile population. Increased stress was observed in women above 35 years and those stopped ‘in cycle’ or during pre-treatment for in-vitro fertilization or frozen embryo transfer. Patient with history of depression or anxiety had a higher prevalence of perceived stress (p= 0.0006). Postponement was perceived as ‘unbearable’ for women experiencing stress (p=0.0032). After the first wave of pandemic, pregnancy desire remained the same and 84.3% of women wanted to resume fertility care as soon as possible. Conclusion: Stopping fertility care during the COVID-19 pandemic had a significant psychological impact on women with an increase of stress, and anxiety. Psychological counseling should always be offered especially during this difficult period.
STUDY QUESTION What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle–Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34–48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26–39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15–26, I2: 0%, fixed-effect) and 33% (95% CI: 25–42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S) This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER CRD42021264042.
Bone morphogenetic protein-15 (BMP15) and growth differentiation factor-9 (GDF9) are oocyte-secreted factors critical for folliculogenesis, oocyte developmental competence and fertility. BMP15 and GDF9 are produced only by gametes and despite known associations with reproductive pathologies (1), concentrations in serum have not previously been reported. We have developed novel immunoassays that allow quantitative measurement of BMP15 and GDF9 in serum and have applied these to samples collected from women undergoing IVF to investigate the possibility that these proteins may be useful biomarkers of female reproductive function. The BMP15 and GDF9 immunoassays were developed in-house and validated for sensitivity (24 and 26 pg/ml, respectively), specificity (<0.01% and <0.03%, respectively) and reproducibility (inter-assay CV <10%). BMP15 and GDF9 were not detectable in a significant number of samples (33% for BMP15; 71% for GDF9) and these were assigned the sensitivity value for subsequent analyses. The effect of superovulation of patients undergoing IVF treatment on serum BMP15 and GDF9 was assessed using samples collected immediately before and on multiple days during FSH stimulation in antagonist treatment cycles (56 bloods from 14 women). BMP15 and GDF9 varied 64-and 15-fold respectively between women, but, within an individual were unchanged throughout superovulation, and were independent of FSH dose (P>0.05). Further analyses including an additional 141 women treated for infertility demonstrated no difference in BMP15 or GDF9 between GnRH antagonist (n=69) and agonist (n=17) stimulation cycles, or between these stimulated cycles and unstimulated cycles (n=41). Serum GDF9 positively correlated with the number of oocytes retrieved from non-PCO/PCOS women after superovulation (r=0.439, P=0.05, n=27), but not in PCO/PCOS patients. Serum GDF9, but not BMP15, was significantly lower in poor responders (women with <4 oocytes retrieved or cycle cancellation due to insufficient follicles on ultrasound (2)), compared with normal responders (27.2±0.8 vs 50.6±7.0 pg/ml; P<0.05). Serum BMP15 and GDF9 did not correlate with age, however BMP15 positively correlated with day 2 baseline FSH (r=0.305, P<0.05, n=52). This is the first report of quantitative measurement of BMP15 and GDF9 levels in human serum, correlating with reproductive potential. Although assay sensitivities require improvement, this study demonstrates the diagnostic potential of oocyte-secreted BMP15 and GDF9 as serum biomarkers in reproductive medicine. References: (1) Persani L et al., HRU 2014; 20(6):869-883. (2) Ferraretti et al., Hum Reprod 2011;26:1616-24. Funding : National Health and Medical Research Council, Australia.
STUDY QUESTION Should testicular sperm extraction (TESE) in non-mosaic 47,XXY Klinefelter syndrome (KS) patients be performed soon after puberty or could it be delayed until adulthood? SUMMARY ANSWER The difference in sperm retrieval rate (SRR) in TESE was not significant between the ‘Young’ (15–22 years old) cohort and the ‘Adult’ (23–43 years old) cohort of non-mosaic KS patients recruited prospectively in parallel. WHAT IS KNOWN ALREADY Several studies have tried to define predictive factors for TESE outcome in non-mosaic KS patients, with very heterogeneous results. Some authors have found that age was a pejorative factor and recommended performing TESE soon after puberty. To date, no predictive factors have been unanimously recognized to guide clinicians in deciding to perform TESE in azoospermic KS patients. STUDY DESIGN, SIZE, DURATION Two cohorts (Young: 15–22 years old; Adult: 23–43 years old) were included prospectively in parallel. A total of 157 non-mosaic 47,XXY KS patients were included between 2010 and 2020 in the reproductive medicine department of the University Hospital of Lyon, France. However 31 patients gave up before TESE, four had cryptozoospermia and three did not have a valid hormone assessment; these were excluded from this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Data for 119 patients (61 Young and 58 Adult) were analyzed. All of these patients had clinical, hormonal and seminal evaluation before conventional TESE (c-TESE). MAIN RESULTS AND THE ROLE OF CHANCE The global SRR was 45.4%. SRRs were not significantly different between the two age groups: Young SRR=49.2%, Adult SRR = 41.4%; P = 0.393. Anti-Müllerian hormone (AMH) and inhibin B were significantly higher in the Young group (AMH: P = 0.001, Inhibin B: P < 0.001), and also higher in patients with a positive TESE than in those with a negative TESE (AMH: P = 0.001, Inhibin B: P = 0.036). The other factors did not differ between age groups or according to TESE outcome. AMH had a better predictive value than inhibin B. SRRs were significantly higher in the upper quartile of AMH plasma levels than in the lower quartile (or in cases with AMH plasma level below the quantification limit): 67.7% versus 28.9% in the whole population (P = 0.001), 60% versus 20% in the Young group (P = 0.025) and 71.4% versus 33.3% in the Adult group (P = 0.018). LIMITATIONS, REASONS FOR CAUTION c-TESE was performed in the whole study; we cannot rule out the possibility of different results if microsurgical TESE had been performed. Because of the limited sensitivity of inhibin B and AMH assays, a large number of patients had values lower than the quantification limits, preventing the definition a threshold below which negative TESE can be predicted. WIDER IMPLICATIONS OF THE FINDINGS In contrast to some studies, age did not appear as a pejorative factor when comparing patients 15–22 and 23–44 years of age. Improved accuracy of inhibin B and AMH assays in the future might still allow discrimination of patients with persistent foci of spermatogenesis and guide clinician decision-making and patient information. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by a grant from the French Ministry of Health D50621 (Programme Hospitalier de Recherche Clinical Régional 2008). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER NCT01918280.
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