A B S T R A C T PurposeGermline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility. Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments. MethodsWe performed ovarian stimulation in 126 women with breast cancer by using letrozole and gonadotropins for the purpose of fertility preservation by embryo or oocyte cryopreservation. As surrogates of ovarian reserve, the oocyte yield and the incidence of low response were compared with ovarian stimulation according to BRCA mutation status. ResultsOf the 82 women who met the inclusion criteria, 47 women (57%) had undergone BRCA testing, and 14 had a mutation in BRCA genes, of which two were of clinically undetermined significance. In BRCA mutation-positive patients, low ovarian response rate was significantly higher compared with BRCA mutation-negative patients (33.3 v 3.3%; P ϭ .014) and with BRCA-untested women (2.9%; P ϭ .012). All BRCA mutation-positive low responders had BRCA1 mutations, but low response was not encountered in women who were only BRCA2 mutation positive. Compared with controls, BRCA1 mutation-but not BRCA2 mutation-positive women produced lower numbers of eggs (7.4 [95% CI, 3.1 to 17.7] v 12.4 [95% CI, 10.8 to 14.2]; P ϭ .025) and had as many as 38.3 times the odds ratio of low response (95% CI, 4.1 to 353.4; P ϭ .001). ConclusionBRCA1 mutations are associated with occult primary ovarian insufficiency. This finding may, at least in part, explain the link between infertility and breast/ovarian cancer risks.

MicroRNAs (miRs) are small molecules important for regulation of transcription and translation. The objective was to identify hormonally regulated miRs in human endometrial stromal cells and to determine the impact of the endocrine disruptor, bisphenol A (BPA), on those miRs. miR microarray analysis and multiple confirmatory cell preparations treated with 17β-estradiol (E2) and BPA altered miR-27b, let-7c, let-7e and miR-181b. Further, decidualization downregulated miR-27b. VEGFB and VEGFC were validated as targets of miR-27b. Identification of miR-27b target genes suggests that BPA and E2 downregulate miR-27b thereby leading to upregulation of genes important for vascularization and angiogenesis of the endometrium during the menstrual cycle and decidualization.

Objective Ovarian and testicular tissue cryopreservation are the only fertility preservation options for sexually immature individuals. Because of their experimental nature, it is important to determine safety and possible bundling with other medicallyindicated procedures. Study design Prospective observational. Results Cryopreservation indications included cancer in 75 % of females and 50 % of males, while non-cancer indications included various hematological conditions. Similar numbers of females (12/28) and males (3/9) underwent prior chemotherapy. Females underwent laparoscopic (27/28) or robotic (1/28) approaches while incisional biopsy was used in males. Bundling of ovarian and testicular harvesting with other medicallyindicated procedures was performed in 42 % and 22 %, respectively. The operative time inclusive of bundled procedures was similar (1.6 ± 0.1 vs. 0.9 ± 0.3 h) but the discharge time was significantly longer for females than males (10.4±0.6 vs. 4.6±0.6 h, p<0.05) due to frequent bundling of medically-indicated procedures in females. All procedures were successfully completed without complications or significant blood loss. Conclusions Pediatric gonadal tissue cryopreservation can be combined with other medically-indicated procedures to minimize the potential inconvenience, additional anesthetic risks, and costs.Keywords Hematology/oncology . Children . Cryopreservation . Fertility preservationCapsule Ovarian and testicular cryopreservation is feasible alone or in combination with other procedures in children.S. Babayev and E. Arslan contributed equally to this work.

As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols.

Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.