Rafael Confino

Understanding Fertility in Young Female Cancer Patients

Young women diagnosed with cancer today have a greater chance of long-term survival than ever before. Successful survivorship for this group of patients includes maintaining a high quality of life after a cancer diagnosis and treatment; however, lifesaving treatments such as chemotherapy, radiation, and surgery can impact survivors by impairing reproductive and endocrine health. Studies demonstrate that future fertility is a concern for many women diagnosed with cancer, but physician knowledge and attitudinal barriers can still prevent females from receiving care. Today, fertility preservation is an option for girls and women facing a cancer diagnosis, and emerging research is providing clinicians with an increasing number of reproductive and hormonal management tools. Physicians can play an important role in fertility by working closely with oncologists, providing patients with information about fertility preservation options prior to the start of cancer treatment, monitoring reproductive capacity after treatment, and working with cancer survivors to explore potential avenues to parenthood.

The impact of fertility preservation on treatment delay and progression-free survival in women with lymphoma: a single-centre experience.

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Practices and Attitudes Regarding Women Undergoing Fertility Preservation: A Survey of the National Physicians Cooperative

PURPOSE To describe physician attitudes and variations in oncofertility treatment strategies. METHODS An exploratory online survey administered between December 1, 2014 and January 27, 2015 to 185 members of the National Physicians Cooperative (NPC). RESULTS Twenty-eight percent (52 of 185) of NPC members responded to the online survey. Fifty percent of respondents were obstetrician-gynecologists working largely in academic medical centers. Thirty-eight percent stated that 14 was the youngest age they felt comfortable performing oocyte retrievals with 35% stating that any age was acceptable as long as they were postpubertal. Short stimulation protocols, utilizing a gonadotropin-releasing hormone (GnRH) antagonist (86%), were more common than long stimulation or microdose Lupron flare protocols (23% and 18%), respectively, which utilize a GnRH agonist. Random start protocols were used by 77% and over 90% perform luteal phase starts. When using random start protocols, 64% use gonadotropins only and 32% start GnRH antagonists alone for several days before starting gonadotropins. Fifty-five percent of physicians were comfortable stimulating ovarian cancer patients only after clearance from an oncologist. Aromatase inhibitors (77%) were significantly more common than tamoxifen (24%) for stimulation in breast cancer patients (p = 0.0006). When considering ovarian stimulation after chemotherapy, 24% expressed comfort only if blood counts are normal, 38% tend to wait 3 months. Regarding experimental treatment, 83% report discussing the use of GnRH agonists alone and 64% of clinics offer ovarian tissue cryopreservation. CONCLUSIONS This study underlines the wide variation that exists in stimulation and phase start techniques, patient selection, comfort levels, and cancer type-specific decision making.

Female Reproductive Aging: From Consequences to Mechanisms, Markers, and Treatments

Abstract Aging is universal and underlies chronic disease as well as tissue and cellular deterioration. The female reproductive system is the first to age in humans, with functional decline occurring decades prior to other organs. Reproductive aging is associated with a decrease in both the number and quality of eggs within the ovary, which together contribute to increased incidences of miscarriages, infertility, and birth defects. Reproductive aging also affects general health because ovarian hormones, such as estrogen, regulate downstream organ systems. The negative consequences of female reproductive aging are becoming more prevalent as women globally are delaying childbearing and more women are living well beyond menopause due to life-extending medical interventions and advances. Here we synthesize data from mouse models and humans to define age-associated changes in endocrinology, gamete quality, and the somatic ovarian environment, and we describe how genetic, lifestyle, and environmental factors accelerate such changes. There is a clinical need to generate tools to assess reproductive aging and to develop methods to improve reproductive outcomes in the setting of advanced reproductive age. The delineation of new biological mechanisms underlying reproductive aging is continuously informing therapeutic interventions, which are largely focused on targeting mitochondrial function. However, the diversity of therapeutic strategies is likely to expand as we learn more about the complex, multifactorial phenomenon of reproductive aging, which will impact every single female.

Retinoid metabolism in endometriosis

Endometriosis is an estrogen-dependent disease in which progesterone resistance and inflammation have been found to be major mechanisms responsible for its development and progression. When compared to eutopic endometrium, key molecules have been found to be differentially expressed, which contribute to these mechanisms. One pathway that is aberrant in endometriotic tissue when compared to eutopic endometrium is the retinoic acid signaling pathway. This review focuses on the role of the retinoid signaling pathway in endometriosis and summarizes evidence that supports the use of retinoid compounds for the stimulation of pro-apoptotic activity in these cells.