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    Association of germline BRCA pathogenic variants with diminished ovarian reserve: A meta-analysis of individual patient-level data
    (American Society of Clinical Oncology, 2021) Turan, Volkan; Lambertini, Matteo; Lee, Dong-Yun; Wang, Erica; Clatot, Florian; Karlan, Beth Y.; Demeestere, Isabelle; Bang, Heejung; Oktay, Kutluk
    PURPOSE: To determine whether germline BRCA (gBRCA) pathogenic variants are associated with decreased ovarian reserve. MATERIALS AND METHODS: An individual patient-level data meta-analysis was performed using five data sets on 828 evaluable women who were tested for gBRCA. Of those, 250 carried gBRCA, whereas 578 had tested negative and served as controls. Of the women with gBRCA, four centers studied those affected with breast cancer (n = 161) and one studied unaffected individuals (n = 89). The data were adjusted for the center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Anti-Müllerian hormone (AMH) levels in affected women were drawn before presystemic therapy. RESULTS: The mean age of women with versus without gBRCA1/2 (34.1 ± 4.9 v 34.3 ± 4.8 years; P = .48) and with gBRCA1 versus gBRCA2 (33.7 ± 4.9 v 34.6 ± 4.8 years; P = .16) was similar. After the adjustments, women with gBRCA1/2 had significantly lower AMH levels compared with controls (23% lower; 95% CI, 4 to 38; P = .02). When the adjusted analysis was limited to affected women (157 with gBRCA v 524 without, after exclusions), the difference persisted (25% lower; 95% CI, 9 to 38; P = .003). The serum AMH levels were lower in women with gBRCA1 (33% lower; 95% CI, 12 to 49; P = .004) but not gBRCA2 compared with controls (7% lower; 95% CI, 31% lower to 26% higher; P = .64). CONCLUSION: Young women with gBRCA pathogenic variants, particularly those affected and with gBRCA1, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.
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    Trends and regional differences for fertil ity preservation procedures in women with breast cancer
    (Elsevier, 2024) Turan, Volkan; Bedoschi, Giuliano; Lee, Dong-Yun; Barbosa, Caio Parente; Oliveira, Renato de; Saçıntı, Koray Görkem; Sönmezer, Murat; Lambertini, Matteo; Massarotti, Claudia; Schaub, Amelia; Wang, Erica; Gayete-Lafuente, Sonia; Dunlop, Cheryl; Anderson, Richard A.; Bang, Heejung; Oktay, Kutluk H.
    Introduction : Breast cancer is the most common malignancy in women of reproductive age and chemotherapy protocols impair fertility, frequently necessitating fertility preservation (FP) referral. Embryo, oocyte, or ovarian tissue cryopreservation are established FP modalities in women with breast cancer but there are few data on their uptake over time. In this study our aim was to determine the regional time trends and utility differences for fertility preservation methods of reproductive tissue cryopreservation. Methods : This multicenter study included 1,623 women diagnosed with breast cancer from seven tertiary centers in six countries (Brazil, Italy, Scotland, South Korea, Turkey, USA). Participant centers provided the details of FP cryopreservation approaches broken down annually from 2012 to 2021. Women with newly diagnosed breast cancer, aged 18-45 years who were referred for FP at participating centers and had normal ovarian function at the time were included. Results : We found a mean increase of 7% per year (p=0.002, adjusting for centers) in the number of women referred for FP. Of those who were referred (n=1623), a mean 38.7% underwent FP (n=629), with a range of 12% in South Korea) to 95% in Brazil. The number of women undergoing ovarian stimulation for FP continually increased until 2021, with oocyte cryopreservation being the most common procedure throughout the study period (p=0.014 for time trend). The proportion of random start ovarian stimulation cycles increased each year from 58.3% in 2012 to 86.8% in 2021, (p=0.005 for time trend, and p=0.04 for 2012 vs. 2021). Conclusions : The utility of FP has steadily increased for young women with breast cancer over the last decade, although regional differences significantly influence FP practices. The findings of our study could have value for policy making in FP care for young women with breast cancer at the local, regional, or global level. Micro abstract Breast cancer is the most common malignancy in women of reproductive age and chemotherapy protocols impair fertility, frequently necessitating fertility preservation referral. The utility of fertility preservation has steadily increased for young women with breast cancer over the last decade, although regional differences significantly influence fertility preservation practices.