Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function

BACKGROUND. Various chemotherapy agents, especially of the alkylating category, have been associated with premature ovarian failure but there is no quantitative evidence of chemotherapy-induced ovarian damage in humans. The aim was to quantify the impact of chemotherapy on primordial follicle reserve and stromal function in human ovary with a prospective controlled quantitative histologic and in vitro study. METHODS. Samples from 26 patients who were undergoing ovarian tissue cryopreservation for fertility preservation were assessed histologically and for in vitro estradiol production. Of the 26 patients, 10 had previously received chemotherapy whereas 16 had not (control). There were 17 age-matched patients. Primordial follicle counts and in vitro estrogen production were compared between age-matched control and chemotherapy patients as well as between those who did and did not receive alkylating agents. RESULTS. Patients who received chemotherapy had significantly lower primordial follicle counts than control patients (5.4 +/- 1.32 vs 9.6 +/- 2.2, P = .05). Furthermore patients treated with alkylating regimens had significantly lower primordial follicle counts compared with those who received nonalkylating agents (2.9 +/- 1.1 vs 7.9 +/- 1.6, P < .05) and with those who did not receive any chemotherapy (2.9 +/- 1.1 vs 9.6 +/- 2.2, P < .05). In vitro, ovarian cortical pieces from individuals who were previously exposed to chemotherapy (chemotherapy group) produced significantly less estradiol compared with those who were not (control group). In the chemotherapy group, there was no difference in in vitro estradiol production between those who received alkylating agents and those who did not. CONCLUSIONS. This is the first quantitative evidence of the impact of chemotherapy on ovarian infrastructure, and shows that, whereas alkylating agents can significantly reduce ovarian reserve, both alkylating and nonalkylating regimens may affect ovarian stromal function

A novel ovarian xenografting model to characterize the impact of chemotherapy agents on human primordial follicle reserve

Many chemotherapeutic agents, especially of the alkylating family, alter fertility in premenopausal females. However, it is not practically possible to quantify and characterize the impact of cancer drugs on ovarian reserve in a clinical setting. Thus, our specific aim was to develop a xenograft model to characterize the in vivo impact of chemotherapy agents on human ovary. Ovarian pieces from 24 weeks old abortuses were xenografted s.c. to severe combined inummodeficient mice (n = 52). Animals received either a single dose of 200 mg/kg of cyclophosphamide or the vehicle. Grafts were recovered from the control and treated mice 12 to 72 h after the cyclophosphamide injection and serially sectioned for primordial follicle counts. Apoptosis was assessed with terminal nucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Platelet/endothelial cell adhesion molecule I (PECAM-1) staining, as well as intra-vital fluorescein-conjugated lectin and Evans blue labeling were done to assess microvasculature by confocal microscopy. Although there was 12% reduction in primordial follicle density by 12 h following treatment (P > 0.05), the follicle loss increased significantly at 24 h (53%, P < 0.01) and peaked at 48 h (93%, P < 0.0001). TUNEL staining peaked at 12 h, earlier than the diminishment in follicle numbers, and decreased thereafter. Xenograft vascularization pattern was similar to non-xenografted tissue, indicating appropriate in vivo drug delivery. The impact of cyclophosphamide on primordial follicle reserve in our human ovarian xenograft model is consistent with the clinical gonadotoxicity of this drug. Human ovarian xenografting is a promising model to characterize the gonadotoxic effects of current and emerging cancer drugs without a need for lengthy clinical studies

Women Shelters as a Social Institution in Struggle against Violence

Violence against women is a social problem. While various public and private measures are taken to eradicate its existence, certain services are provided to protect women who have been already exposed to violence and to help them adopt a sustainable life thereafter through public and/or private institutions and organizations. Within this framework, "women's shelters" in Turkey provide temporary services to victims of violence against women by rescuing them from violence, solving psycho-social and economic problems and preparing them for a better future. In this context, the aim of the research is to determine the roles and functions of the shelters in the struggle against violence against women. Descriptive research design was used in the research. In-depth interviews were conducted with 25 women staying in three shelters in Izmir province affiliated to the General Directorate on the Status of Women, Ministry of Family, Labor and Social Services of the Republic of Turkey. The data obtained from these interviews were deciphered and analysed with MAXQDA 18 qualitative data analysis program. In the light of the data obtained from one-on-one interviews, seven main themes were revealed. These themes are as follows: (i) the nature of violence against women, (ii) causes of violence against women, (iii) the societal support to the women victims of violence, (iv) the role of a "women's shelter" in struggling violence against women, (v) conditions of the "women shelters", (vi) sustainable living of women post-shelter and (vii) further suggestions for the improvements of "women shelters"

Breast cancer diagnosis following ovarian stimulation: Are the tumours different?

WOS: 000281172300016PubMed: 20615755Demographic data and tumour characteristics of 18 patients (study group) diagnosed with breast cancer within 24 months of undergoing ovarian stimulation with either gonadotrophins or clomiphene citrate were evaluated and compared with similar 102 age-matched women diagnosed with breast cancer without prior infertility treatment (control group). Eight out of 17 (47.1%) patients in the study group and 35/95 (36.8%) patients in the control group had positive family history for breast cancer. Median tumour size was similar in the study and control groups (both 1.3 cm). Both groups were comparable regarding tumour histological types and oestrogen receptor, progesterone receptor and Her2/Neu expression status. Albeit not significant, stage 0 tumours were more prevalent in the study group compared with the control group (22.2% versus 10.5%), and there were no stage III tumours in the study group as opposed to 7/95 in the control group. In conclusion, breast cancer diagnosed within the first 2 years following infertility treatment is similar in tumour characteristics compared with those occurring in patients without prior infertility treatment. (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved

Menstrual cycle characteristics of young females with occult primary ovarian insufficiency at initial diagnosis and one-year follow-up with serum amh level and antral follicle count

<div><p>Occult primary ovarian insufficiency (also known as incipient ovarian failure or diminished ovarian reserve) is defined as serum AMH level ≤1.1ng/mL in women under age 30. Limited data is available regarding the prevalence of occult POI, the preceding menstrual characteristics and its natural course in otherwise healthy young females. We aimed in this prospective observational study to determine the prevalence of occult POI in young females (< age 30) screened with serum AMH measurement; and analyze the patterns of change in their menstruation at initial assessment and one-year follow-up in relation to the changes in ovarian reserve quantitatively assessed with AMH and AFC. 963 young female college students under age 30 voluntarily participated in this study. 43 of them (4.4%) were diagnosed with occult POI as their AMH levels were ≤ 1.1ng/mL. Thirty-eight (83.4%) of them have regular cycles and denied any menstrual irregularity in the last 12 months. This rate was not statistically different from 7.3% of those with AMH>1.1ng/mL who reported at least one abnormal menstrual cycle in the last year (p = 0.36). Cycle length was significantly shorter in females with AMH ≤ 1.1ng/mL compared to those with AMH>1.1ng/mL (25.1±3.2 vs. 31.2±2.8 respectively, p<0.001). Karyotype, FMR-1 mutation analyses and auto-antibody screening returned normal in all. At one-year follow-up AMH, AFC and mean cycle length were further reduced compared to their values at initial assessment. Now, a greater proportion of the participants with occult POI were menstruating regularly at every 21 days compared to the initial evaluation one year ago (39.5% vs. 13.9% respectively, p = 0.013). Twenty-five underwent oocyte cryopreservation. These findings underscore the importance of screening young females with AMH for possible occult POI. It also emphasizes that young females with critically diminished ovarian reserve may continue to menstruate regularly without any characteristic menstrual abnormality other than shortening of cycle length.</p></div