Fertility Sparing Surgery for Localized Ovarian Cancers Maintains an Ability to Conceive, but is Associated With Diminished Reproductive Potential.

BACKGROUND: Little is known about fertility outcomes after fertility sparing surgery (FSS) for localized ovarian cancers. METHODS: A random sample of 783 women treated for ovarian cancer were identified from the California Cancer Registry for survey (age 18-40 years at diagnosis; diagnosed from 1993-2007). We evaluated outcomes including post-treatment amenorrhea, infertility, early menopause (age <45), and disease recurrence. Logistic regression was used to determine the probability of amenorrhea, infertility, and recurrence. Censored data methods were used to determine the probability of early menopause. RESULTS: A total of 382 women replied. One hundred and sixteen and 266 completed our survey. Two hundred and forty-five reported treatment with potential to impact fertility (i.e., systemic chemotherapy ± radiation/surgery to the abdomen/pelvis). A total of 125 had disease/stage eligible for FSS and 82 (66%) underwent FSS. While many who attempted conception did conceive, 32% did not. Younger age at diagnosis was associated with higher rates of early menopause (P < 0.001) after FSS. Recurrence rates for those undergoing FSS were 8-10%, while none of the women who underwent non-FSS surgery had a recurrence. CONCLUSIONS: FSS maintains an ability to conceive for most patients. However, after FSS, there may be risks of infertility, early menopause with earlier age of treatment, and increased probability of disease recurrence.

Racial, socioeconomic, and demographic disparities in access to fertility preservation in young women diagnosed with cancer.

BACKGROUND: This study seeks to examine the relation between sociodemographic characteristics and the utilization of fertility preservation services in reproductive age women diagnosed with cancer. METHODS: A total of 1041 women diagnosed with cancer between the ages of 18 and 40 years responded to a retrospective survey on demographic information and reproductive health history. Five cancer types were included: leukemia, Hodgkin disease, non-Hodgkin lymphoma, breast cancer, and gastrointestinal cancer. Nine hundred eighteen women reported treatment with potential to affect fertility (chemotherapy, pelvic radiation, pelvic surgery, or bone marrow transplant). Student t test, linear regression, and multivariate logistic regression were used where appropriate to determine the relation between sociodemographic characteristics and the odds of using fertility preservation services. RESULTS: Sixty-one percent of women were counseled on the risk of cancer treatment to fertility by the oncology team. Overall, 4% of women pursued fertility preservation. In multivariate analysis, women who had not attained a bachelor's degree (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5-0.9) were less likely to be counseled. Trends also suggested possible disparities in access to fertility preservation with age older than 35 years (OR, 0.1; 95% CI, 0.0-1.4) or previous children (OR, 0.3; 95% CI, 0.1-1.1) at diagnosis. Disparities in access to fertility preservation based on ethnicity and sexual orientation were also observed. CONCLUSIONS: Sociodemographic health disparities likely affect access to fertility preservation services. Although awareness of fertility preservation has improved in the past decade, an unmet need remains for reproductive health counseling and fertility preservation in reproductive age women diagnosed with cancer.

Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer.

BACKGROUND: The post-treatment quality of life (QOL) impacts of receiving precancer-treatment infertility counseling and of pursuing fertility preservation have not been described in large-scale studies of reproductive age women with cancer. METHODS: In total, 1041 women who were diagnosed between ages 18 and 40 years responded to a retrospective survey and reported whether they received infertility counseling before cancer treatment and whether they took action to preserve fertility. Five cancer types were included: leukemia, Hodgkin disease, non-Hodgkin lymphoma, breast cancer, and gastrointestinal cancer. Validated QOL scales were used: the Decision Regret Score, the Satisfaction with Life Scale (SWLS), and the brief World Health Organization QOL questionnaire. RESULTS: Overall, 560 women (61%) who received treatment that potentially could affect fertility were counseled by the oncology team, 45 (5%) were counseled by fertility specialists, and 36 (4%) took action to preserve fertility. Pretreatment infertility counseling by a fertility specialist and an oncologist resulted in lower regret than counseling by an oncologist alone (8.4 vs 11.0; P < .0001). The addition of fertility preservation (6.6 vs 11.0; P < .0001) also was associated with even lower regret scores than counseling by an oncologist alone. Further improvements also were observed in SWLS scores with the addition of fertility specialist counseling (23.0 vs 19.8; P = .09) or preserving fertility (24.0 vs 19.0; P = .05). CONCLUSIONS: Receiving specialized counseling about reproductive loss and pursuing fertility preservation is associated with less regret and greater QOL for survivors, yet few patients are exposed to this potential benefit. Women of reproductive age should have expert counseling and should be given the opportunity to make active decisions about preserving fertility.

Acute ovarian failure underestimates age-specific reproductive impairment for young women undergoing chemotherapy for cancer.

BACKGROUND: The authors sought to describe the age-specific impact of infertility and early menopause after chemotherapy among reproductive age women with cancer. METHODS: A total of 1041 women diagnosed with cancer between the ages of 18 and 40 years responded to a retrospective survey on reproductive health history. Five cancer types were included: leukemia, Hodgkin disease (HD), non-Hodgkin lymphoma (NHL), breast cancer, and gastrointestinal(GI) cancer. Survey questions addressed acute ovarian failure (cessation of menses after treatment), early menopause (menopause before 45 years old), and infertility (failed conception). Logistic regression was used to determine the proportions of acute ovarian failure and infertility based on age at diagnosis. Censored data methods were used to determine the probability of early menopause. RESULTS: Six hundred twenty women received chemotherapy alone. The percentage reporting acute ovarian failure was 8%, 10%, 9%, and 5% for HD, NHL, breast cancer, and GI cancer, respectively. Acute ovarian failure increased significantly with age at diagnosis (P < .05). In subjects not reporting acute ovarian failure, the incidence of infertility was at least 40% at age 35 years and increased significantly with age at diagnosis in HD and breast cancer (P < .05). The estimated probability of early menopause was at least 25% at age 30 years and increased significantly with younger age at diagnosis in HD, NHL, and GI cancer (P < .05). CONCLUSIONS: For patients to receive appropriate counseling, it is important that they understand the potential increased risk of infertility and early menopause beyond that of acute ovarian failure. These findings can provide improved, age-specific counseling regarding reproductive impairment for young women diagnosed with cancer.

Structural organization of WrbA in apo- and holoprotein crystals.

Two previously reported holoprotein crystal forms of the flavodoxin-like E. coli protein WrbA, diffracting to 2.6 and 2.0 A resolution, and new crystals of WrbA apoprotein diffracting to 1.85 A, are refined and analysed comparatively through the lens of flavodoxin structures. The results indicate that differences between apo- and holoWrbA crystal structures are manifested on many levels of protein organization as well as in the FMN-binding sites. Evaluation of the influence of crystal contacts by comparison of lattice packing reveals the protein's global response to FMN binding. Structural changes upon cofactor binding are compared with the monomeric flavodoxins. Topologically non-equivalent residues undergo remarkably similar local structural changes upon FMN binding to WrbA or to flavodoxin, despite differences in multimeric organization and residue types at the binding sites. Analysis of the three crystal structures described here, together with flavodoxin structures, rationalizes functional similarities and differences of the WrbAs relative to flavodoxins, leading to a new understanding of the defining features of WrbAs. The results suggest that WrbAs are not a remote and unusual branch of the flavodoxin family as previously thought but rather a central member with unifying structural features.