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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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    Fertility preservation in breast cancer patients
    (Springer, 2022) Marin, Loris; Turan, Volkan; Oktay, Kutluk
    Breast cancer is the most common malignancy in women as it currently represents 15.2% of all new cancer cases in the United States with 268,600 estimated new cases in 2019 [1]. Under 45 years of age, the percentage of new cases is 10.3% as it is the most common of all in women of childbearing age. Due to the increasingly advanced diagnostic and therapeutic techniques, the mortality rate remains low in recent years. For stages I and II, the 5-year survival is estimated to be respectively 95% and 85–70% (depending on whether they are IIA and IIB), while in advanced stages, survival rates are between 18 and 52% (for stages IIIA and B) [1]. Because the number of young cancer survivors is increasing and as women tend to have children in later reproductive ages, increasing attention has been paid to chemotherapy-related ovarian toxicity [2]. Most women with breast cancer are likely to undergo neoadjuvant or adjuvant chemotherapy that may result in premature ovarian failure and infertility [3–5].
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    Ovarian stimulation and PGT-A outcomes with random start letrozole protocol for fertility preservation in breast cancer patients
    (Oxford University Press, 2022) Arkfeld, Christopher; Gayete-Lafuente, Sonia; Turan, Volkan; Oktay, Kutluk
    Study question Data on random start letrozole ovarian stimulation (RSL) in breast cancer patients is scant. We studied RSL outcomes from a single-center with fertility preservation expertise. Summary answer RSL appears to result in high oocyte and embryo/blastocyst yield, with an age-appropriate aneuploidy rate.
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    Preoperative evaluation and preparation for ovarian tissue transplant surgery
    (Elsevier, 2022) Oktay, Kutluk; Turan, Volkan
    Ovarian tissue cryopreservation is a fertility preservation method which is no longer experimental. The number of healthy babies born with this technique is approaching 200 worldwide. It is the only option for preserving fertility in prepubertal girls and when women have time constraints to undergo ovarian stimulation before chemotherapy. The success of ovarian tissue transplantation surgery is contingent on many interactive factors. A sound, evidence-based preoperative evaluation and preparation of women for ovarian transplantation surgery represents one of the key determinants of success with this procedure. In this chapter, we discuss steps of preoperative evaluation and preparation for a safe and successful ovarian autotransplantation.