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.
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.
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