Breast cancer after IVF: Can ovary stimulation and follicular response affect prognostic factors?

e12538 Background: The ovary stimulation and the follicular response is related with estradiol level. Study in breast cancer patients after IVF if ovarian response or number of IVF cycles affects the prognostic factors. Methods: Patients with breast cancer who underwent IVF are studied the prognostic factors (Ki67, HER2, estrogen receptor (ER), progesterone receptor (PR), oncogene p53, histologic grade) in relation to the ovary response and number of IVF cycles. Results: 73 patients with breast cancer after IVF are studied. They performed 135 cycles of IVF, 36 (49’3%) with 1 IVF and 37 (50’7%) with more than one IVF. Hyper response was present in at least one IVF in 24 (32.9%) patients and there was no hyper response in any IVF in 49 (67.1%) patients. The prognostic factors were: Ki 67> 20 in 31'91% (15/47) Ki 67 <20 in 68'08% (32/47), HER2 + 31'94% (23/72) HER2- 68'05% (49/72), p53 + 45'09% (23/51), p53-54'90% (28/51), HG II-III 56'36% (31/55), HG I 43'63% ( 24/55), RE + 87'5% (63/72), RE- 12'5% (9/72), RP + 76'38% (55/72), RP- 23'61% (17/72). None of prognostic factors varied with the ovary response (hyper response in at least one IVF cycle, normal response, normal or low response) (p=ns). The only prognostic factor that varied with the IVF number was p53 +. Patients with p53 + (23/51), 7 (30’43%) has one IVF, and 16 (69’53%) have more one IVF (p<0’05). Conclusions: In breast cancer after IVF, the ovary stimulation and the follicular response not affect Ki67, HER2, estrogen receptor, progesterone receptor, p53, and histologic grade. p53 positive is more frequent in patients with more than one IVF.

Effects of calcium-vitamin D and metformin on the menstrual cycle and ovulation in polycystic ovary syndrome patients in a tertiary care teaching hospital

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous hormonal disorder of reproductive aged women characterized by chronic anovulation, irregular menstrual cycles and hyperandrogenism. The present study aimed to investigate the effects of metformin and calcium-vitamin D on follicular maturation and regularity of menstrual cycles in patients with PCOS.Methods: A prospective, open-label, multiple arms, randomized clinical trial. Group 1 participants received 1,000 mg of calcium and 400 IU of vitamin D per day, orally, group 2 participants received 1,500 mg of metformin per day, orally and group 3 participants received combination of above drugs. The patients were treated for 3 months and followed up for a further 3 months. Menses regularity, number of dominant follicles (≥14 mm) and pregnancy rates were compared among the three groups.Results: A total of sixty infertile women with PCOS were recruited. Calcium-vitamin D plus metformin treated patients showed highest percentage improvement (50%) menstrual regularity as compared to other two groups (p<0.001) also showed significant follicular response (p<0.014). Calcium-vitamin D plus metformin treated group showed better follicular response in the second and third month of follow-up and 30% of women showed high quality dominant large (≥14 mm) follicles at the end of follow-up period.Conclusions: Calcium-vitamin D plus metformin combination is more effective in terms of follicle maturation and restoring menstrual disturbances as compared to individual drug treatment.

Defining the gonadotrophin requirement for the selection of a single dominant follicle in cattle

The aim was to define the pattern and physiological concentrations of FSH and LH required for the selection of a single dominant follicle in mono-ovulatory species. A series of five experiments was carried out using gonadotrophin-releasing hormone agonist-induced hypogonadal heifers. Animals were infused with different patterns of either FSH and/or LH followed by an ovulatory dose of human chorionic gonadotrophin. Follicular response was monitored by ultrasound scanning and blood samples were collected to measure concentrations of FSH, LH, oestradiol and progesterone. The main findings were: (1) physiological concentrations of FSH given as a continuous infusion and for an adequate duration, in the presence of basal LH, with or without LH pulses, are capable of inducing a superovulatory response, (2) initial exposure to FSH followed by LH pulses alone stimulate the development of multiple preovulatory follicles, confirming that ovarian follicles are capable of transferring dependence on gonadotrophins from FSH to LH, (3) while LH pulses appear not to have a major effect on the pattern of preovulatory follicle development, adequate LH pulsatile support is required for full oestradiol synthesis and (4) the duration of initial exposure to FSH and the ability to transfer the dependence from FSH to LH are critical for the selection of a single dominant follicle. In conclusion, this experimental series confirms that the duration of initial exposure to FSH and the ability of the selected follicle to transfer its gonadotrophic dependence from FSH to LH are critical for the selection of a single dominant follicle in cattle.

Cxcr4 desensitization is an essential regulatory mechanism controlling the extra-follicular B cell response

The signaling axis formed by the chemokine CXCL12 and its receptor CXCR4 plays an important role in B cell development and activation and is finely regulated by a process termed desensitization. Mutations leading to a truncation of the C-terminus tail of CXCR4 and thus to a defective desensitization have been reported in two diseases, a rare immunodeficiency called the WHIM syndrome and a B cell plasmacytoma called Waldenstrom’s Macroglobulinemia (WM). How CXCR4 desensitization may impact B cell activation in the context of a T-independent extra-follicular response is still unknown. Here using a unique mouse model bearing an orthologous gain of function mutation of Cxcr4 we report that Cxcr4 desensitization is an essential gatekeeper controlling B lymphocyte entry into cycle, plasma cell differentiation, migration and maturation upon Myd88-dependent signaling. Altogether, our results support an essential role for Cxcr4 desensitization in limiting the depth and width of the B cell extra-follicular response and PC development.