Jennifer E. Mersereau

Liquiritigenin is a plant-derived highly selective estrogen receptor β agonist

After the Womens Health Initiative found that the risks of hormone therapy outweighed the benefits, a need for alternative drugs to treat menopausal symptoms has emerged. We explored the possibility that botanical agents used in Traditional Chinese Medicine for menopausal symptoms contain ERbeta-selective estrogens. We previously reported that an extract containing 22 herbs, MF101 has ERbeta-selective properties. In this study we isolated liquiritigenin, the most active estrogenic compound from the root of Glycyrrhizae uralensis Fisch, which is one of the plants found in MF101. Liquiritigenin activated multiple ER regulatory elements and native target genes with ERbeta but not ERalpha. The ERbeta-selectivity of liquiritigenin was due to the selective recruitment of the coactivator steroid receptor coactivator-2 to target genes. In a mouse xenograph model, liquiritigenin did not stimulate uterine size or tumorigenesis of MCF-7 breast cancer cells. Our results demonstrate that some plants contain highly selective estrogens for ERbeta.

Pretreatment antimüllerian hormone levels determine rate of posttherapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy

OBJECTIVE To identify factors associated with ovarian reserve impairment during and immediately after chemotherapy. DESIGN Prospective cohort study. SETTING Four university hospitals. PATIENT(S) Forty-six adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Measurements of ovarian reserve via levels of serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, and antimüllerian hormone (AMH) as well as antral follicle counts and mean ovarian volume at 3-month intervals. RESULT(S) Changes in ovarian reserve were quantified for both the acute impact of treatment using linear regression and the longitudinal recovery after therapy using mixed-effects models adjusted for baseline ovarian reserve, use of alkylating agent, and hormone use. The women had at least one pretreatment and two posttreatment study visits (mean follow-up interval: 12 months). All measures of ovarian reserve demonstrated statistically significant changes during chemotherapy. Alkylating agent exposure and baseline ovarian reserve were acutely associated with the magnitude of impairment, and pretreatment AMH levels were associated with the rate of recovery of AMH after treatment. In adjusted models, participants with a pretreatment AMH level > 2 ng/mL recovered at a rate of 11.9% per month after chemotherapy, whereas participants with pretreatment AMH levels ≤ 2 ng/mL recovered at a rate of 2.6% per month after therapy. CONCLUSION(S) Baseline ovarian reserve and alkylating agent exposure effect the magnitude of acute changes in ovarian reserve from chemotherapy. The rate of recovery of AMH is impacted by pretreatment levels. This should be considered during pretreatment fertility preservation counseling.

To preserve or not to preserve: how difficult is the decision about fertility preservation?

The decision to pursue fertility preservation (FP) after a cancer diagnosis is complex. We examined the prevalence of high decisional conflict and specific factors that influence this decision using the Decisional Conflict Scale (DCS).

Trends of socioeconomic disparities in referral patterns for fertility preservation consultation

BACKGROUND While oncologists are aware that cancer treatments may impact fertility, referral rates for fertility preservation consultation (FPC) remain poor. The goal of this study was to identify predictors associated with FPC referral. METHODS This is a retrospective, cohort study of women aged 18-42 years diagnosed with a new breast, gynecologic, hematologic or gastrointestinal cancer at our institution between January 2008 and May 2010. Exclusion criteria included history of permanent sterilization, documentation of no desire for future children, stage IV disease, short interval (<4 days) between diagnosis and treatment and treatment that posed no threat to fertility. Demographic, socioeconomic and cancer variables were evaluated with respect to FPC. Logistic regression was used to determine the odds of referral for FPC based on specified predictors. RESULTS One hundred and ninety-nine patients were eligible for FPC and of those, 41 received FPC (20.6%). Women with breast cancer were 10 times more likely to receive FPC compared with other cancer diagnoses [odds ratio (OR) 10.1; 95% confidence interval (CI) 3.8-26.8]. The odds of FPC referral were approximately two times higher for Caucasian women (OR 2.4; 95% CI 0.9-6.2), three times higher for age <35 years (OR 3.3; 95% CI 1.4-7.7) and four times higher in nulliparous women (OR 4.6; 95% CI 1.9-11.3). There was no association between BMI, income, distance to our institution, being in a relationship and referral for FPC. CONCLUSIONS Overall referral rates for FPC are low, and there appear to be significant discrepancies in referral based on ethnicity, age, parity and cancer type. This highlights a need for further provider education and awareness across all oncologic disciplines.

Optimal timing for elective egg freezing

OBJECTIVE To estimate the optimal age to pursue elective oocyte cryopreservation. DESIGN A decision-tree model was constructed to determine the success and cost-effectiveness of oocyte preservation versus no action when considered at ages 25-40 years, assuming an attempt at procreation 3, 5, or 7 years after initial decision. SETTING Not applicable. PATIENT(S) Hypothetical patients 25-40 years old presenting to discuss elective oocyte cryopreservation. INTERVENTION(S) Decision to cryopreserve oocytes from age 25 years to age 40 years versus taking no action. MAIN OUTCOME AND MEASURE(S) Probability of live birth after initial decision whether or not to cryopreserve oocytes. RESULT(S) Oocyte cryopreservation provided the greatest improvement in probability of live birth compared with no action (51.6% vs. 21.9%) when performed at age 37 years. The highest probability of live birth was seen when oocyte cryopreservation was performed at ages <34 years (>74%), although little benefit over no action was seen at ages 25-30 years (2.6%-7.1% increase). Oocyte cryopreservation was most cost-effective at age 37 years, at

Fertility preservation: a pilot study to assess previsit patient knowledge quantitatively

28,759 per each additional live birth in the oocyte cryopreservation group. When the probability of marriage was included, oocyte cryopreservation resulted in little improvement in live birth rates. CONCLUSION(S) Oocyte cryopreservation can be of great benefit to specific women and has the highest chance of success when performed at an earlier age. At age 37 years, oocyte cryopreservation has the largest benefit over no action and is most cost-effective.

Gonadal Failure with Cyclophosphamide Therapy for Lupus Nephritis: Advances in Fertility Preservation

OBJECTIVE To provide a quantitative assessment of patient knowledge about fertility and fertility preservation treatment options before the initial fertility preservation consultation at a university-based fertility preservation center. DESIGN Prospective pilot survey containing 13 items assessing patient knowledge about fertility preservation, including the available treatment options and their requirements, success rates, and associated risks. SETTING University-based IVF center. PATIENT(S) Women aged 18 to 41 years with illnesses requiring treatments posing a serious threat to future fertility who were referred for fertility preservation consultation between April 2009 and June 2010. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Knowledge score. RESULT(S) Forty-one eligible patients were identified, and all completed surveys before their consultation. A knowledge score was generated for each patient with 1 point awarded for each correct answer. Overall, patients had poor previsit fertility preservation knowledge (mean score 5.9±2.7). Higher knowledge scores were correlated with personal experience with infertility and previous exposure to fertility preservation treatment information. There was no correlation between knowledge score and age, relationship status, pregnancy history, education, or income. CONCLUSION(S) Patients seen for fertility preservation consultation at our university-based center generally tend to be in their early 30s, white, well educated, and married. Previsit knowledge about fertility preservation treatment options was poor and did not correlate with age, education, and relationship status.

Uterine septum: a guideline

Intravenous cyclophosphamide remains an important therapy for patients with severe systemic lupus erythematosus--including lupus nephritis, which primarily affects women in their reproductive years. As prognosis improves, the chronic toxicity of this therapy assumes greater importance. This article reviews cyclophosphamide use, its effect on gonadal function, and protection of gonadal reserve during therapy. Egg, embryo, or gonadal tissue cryopreservation and alternative therapeutic strategies are considered.

Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline

The purpose of this guideline is to review the literature regarding septate uterus and determine optimal indications and methods of treatment for it. Septate uterus has been associated with an increase in the risk of miscarriage, premature delivery, and malpresentation; however, there is insufficient evidence that a uterine septum is associated with infertility. Several studies indicate that treating a uterine septum is associated with an improvement in live-birth rates in women with a history of prior pregnancy loss, recurrent pregnancy loss, or infertility. In a patient without infertility or prior pregnancy loss, it may be reasonable to consider septum incision following counseling regarding potential risks and benefits of the procedure. Many techniques are available to surgically treat a uterine septum, but there is insufficient evidence to recommend one specific method over another.

Building a successful fertility preservation program at a major cancer center.

Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to identify who is at high risk, how to prevent OHSS, and the treatment for existing OHSS.