Looking beyond the ovary for oncofertility care in women: uterine injury as a potential target for fertility-preserving treatments.

Treatment for cancer has the potential to significantly diminish fertility and, further, to negatively impact the obstetrical outcomes of pregnancies that do occur. Cancer survivors have decreased rates of fertility and increased rates of pregnancy complications, such as preterm birth and low birth weight, after exposure to chemotherapy. To date, research on the impact of chemotherapy and radiotherapy on fertility and pregnancy outcomes has focused largely on the gonadotoxic effect of cancer treatments on ovaries, while the uterus and endometrium have not been extensively studied. It is intuitive, however, that decreased fertility and poorer obstetrical outcomes may be substantially mediated through injury to a highly mitotic tissue like the endometrium, which is also central to embryo implantation and utero-placental exchange. Pregnancy complications in cancer survivors might be due to compromised blood supply to the endometrium and myometrium affecting placentation or altered remodeling of the pregnant uterus secondary to radiation fibrosis. Alterations in endometrial receptivity at the molecular level could affect pregnancy implantation and early pregnancy loss, but later complications also can occur. This review focuses on understanding the unintended effects of chemotherapy and radiotherapy on uterine function in female cancer survivors and the impact on pregnancy, and summarizes mechanisms to protect and treat the uterus before and after cancer chemotherapy and radiotherapy.

Antral follicle count recovery in women with menses after treatment with and without gonadotropin-releasing hormone agonist use during chemotherapy for breast cancer.

PURPOSE: After chemotherapy for breast cancer, most women will recover some ovarian function, but the timing and extent of this recovery are poorly understood. We studied post-chemotherapy ovarian recovery in women with and without a history of ovarian suppression during chemotherapy. METHODS: Reproductive age breast cancer patients who were seen prior to chemotherapy for fertility preservation consult were consented for follow-up ovarian function assessment (every 3-6 months after chemotherapy) with antral follicle count (AFC) in this prospective cohort study. We restricted our analysis to those with menses present after chemotherapy. Box plots were used to demonstrate the change in follow-up AFC versus time elapsed after chemotherapy. A mixed effects regression model was used to assess differences in AFC. RESULTS: Eighty-eight patients with a history of newly diagnosed breast cancer were included. Forty-five patients (51%) had ovarian suppression with GnRH agonist (GnRHa) during chemotherapy. AFC recovery appeared to plateau at 1 year after completing chemotherapy at a median of 40% of pre-chemotherapy AFC. After adjustment for age, initial AFC, cyclophosphamide exposure, combined hormonal contraceptive (CHC) use, and tamoxifen use, AFC recovered faster and to a greater degree for those women who underwent GnRHa therapy for ovarian protection during chemotherapy (P = 0.032). CONCLUSIONS: Women with menses after chemotherapy for breast cancer appear to recover their full potential AFC 1 year after their last chemotherapy dose. Treatment with GnRHa during chemotherapy is associated with a higher degree of AFC recovery. The findings of this study can aid in counseling patients prior to chemotherapy about expectations for ovarian recovery and planning post-treatment fertility preservation care to maximize reproductive potential when pre-treatment fertility preservation care is not possible or has limited oocyte yield.

The role of in-depth reproductive health counseling in addressing reproductive health concerns in female survivors of nongynecologic cancers.

The purpose of this study was to characterize reproductive concerns among female cancer survivors and determine the role of targeted counseling in improving overall reproductive quality of life (QOL). A survey was administered to women from the California Cancer Registry, ages 18-40, with nongynecologic cancers diagnosed from 1993 to 2007, who received fertility-compromising treatments. In total, 356 women completed the survey, which included questions regarding their reproductive health counseling history and the reproductive concerns scale (RCS), a validated reproductive QOL tool. Factors independently associated with higher RCS scores included a desire for children at the time of diagnosis, posttreatment infertility, treatment with chemoradiation or bone marrow transplant, and income less than $100,000 per year at diagnosis. Among the highest reported reproductive concerns were those related to loss of control over one's reproductive future and concerns about the effect of illness on one's future fertility. Across our population and independent of age, in-depth reproductive health counseling prior to cancer treatment was associated with significantly lower RCS scores. Our findings highlight the importance of early counseling and targeting high-risk groups for additional counseling after completion of cancer treatment. This approach may be an effective strategy for optimizing long-term reproductive QOL in this vulnerable population.

Comparison of a new, rapid enzyme-linked immunosorbent assay with latex particle agglutination for the detection of Haemophilus influenzae type b infections.

A new, rapid enzyme-linked immunosorbent assay (ELISA) for the detection of polyribosylribitol phosphate of Haemophilus influenzae type b was compared with a commercially available latex particle agglutination (LPA) system (Bactigen; Wampole Laboratories, Cranbury, N.J.). By adding specimens and the anti-polyribosylribitol phosphate immunoglobulin-enzyme conjugate to the solid phase in a single step, it was possible to complete the ELISA procedure in 30 min. The ELISA was capable of detecting 0.3 ng of polyribosylribitol phosphate per ml in cerebrospinal fluid, 0.6 ng/ml in urine, and 1.2 ng/ml in serum; the in vitro sensitivity of LPA in these body fluids was 0.6, 0.3, and 0.3 ng/ml, respectively. Both procedures detected polyribosylribitol phosphate in specimens from 25 patients with bacteriologically confirmed H. influenzae type b infections. The specificity of ELISA appeared to be superior to that of LPA. ELISA was positive in only one of seven patients who had a positive LPA test and a clinical illness that was not compatible with haemophilus infection. Moreover, five patients with bacteriologically confirmed infections due to other pathogens (Streptococcus pneumoniae type 14 [two patients], Neisseria meningitidis group C, Escherichia coli K100, and Staphylococcus aureus) had false-positive LPA tests; only two (E. coli and S. aureus) were positive by ELISA. A total of 108 samples from 61 patients who had no evidence of haemophilus infections were negative by both procedures. The ELISA is a rapid, sensitive, and specific alternative to LPA for the detection of haemophilus polyribosylribitol phosphate.

Multicenter evaluation of a new enzyme immunoassay for detection of Clostridium difficile enterotoxin A.

The Premier Clostridium difficile toxin A enzyme immunoassay (PTA EIA) (Meridian Diagnostics, Inc., Cincinnati, Ohio) for rapid diagnosis of antibiotic-associated colitis (AAC) was evaluated in a multicenter study. Stool samples from 421 patients suspected of having AAC were tested for toxin A by the PTA EIA and for toxin B by three tissue culture assays (TCA) employing WI-38 cells (New England Deaconess Hospital) in conventional tubes or foreskin fibroblasts (Children's Hospital) or Vero cells (Beth Israel Hospital) in microwells. The tubes and plates were examined at 24 and 48 h for cytotoxicity. Clinical criteria, repeat testing at another site, and culture of frozen stool samples for C. difficile were used to evaluate discrepant results. Of 504 samples, 66 were positive and 409 were negative by both tests. Eight samples had indeterminate PTA EIA results and were excluded from this analysis. Of 21 discrepancies, 9 were PTA EIA positive and TCA negative and 12 were PTA EIA negative TCA positive. Following resolution of the discrepancies, 11 of 12 PTA EIA-negative-TCA-positive and 5 of 9 PTA EIA-positive-TCA-negative samples were considered true positive for AAC. The sensitivity and specificity were, respectively, 86.6 and 99.0% for the PTA EIA and 93.9 and 99.8% for TCA. The predictive values of positive and negative tests were, respectively, 94.7 and 97.4% for the PTA EIA and 98.7 and 98.8% for TCA. We conclude that the PTA EIA is a rapid, simple EIA technique whose accuracy in detecting enterotoxin A approaches that of reference TCA methods for detection of cytotoxin B.