Options for Fertility Preservation in Children.

Fertility preservation therapies can conserve future reproductive potential for persons facing serious medical diagnoses. With cure rates for childhood cancer reaching almost 80%, quality-of-life concerns for long-term survivors, including future parenting, are becoming more pertinent. Late effects of childhood cancer can be divided into physical, social, psychological, and spiritual domains. Potential loss of fertility threatens the well-being of these children in all these domains. Providers often hesitate to discuss fertility preservation with the patients. However, parental attitudes toward discussion of fertility preservation have been found to be open to such conversations for both prepubertal and postpubertal children who have a cancer diagnosis. Multiple national and international organizations recommend discussion with all persons having gonadotoxic therapy, including children, regarding the effect of planned treatment on future fertility and their options for fertility preservation. Renal or rheumatologic disease treated with high-dose cyclophosphamide and chromosomal anomalies such as Turner or Klinefelter syndrome may be amenable to fertility preservation. This essay reviews fertility preservation options available to children, as well as the expanding list of indications for fertility preservation.

Predictors of medical school clerkship performance: a multispecialty longitudinal analysis of standardized examination scores and clinical assessments.

BACKGROUND: Evidence suggests that poor performance on standardized tests before and early in medical school is associated with poor performance on standardized tests later in medical school and beyond. This study aimed to explore relationships between standardized examination scores (before and during medical school) with test and clinical performance across all core clinical clerkships. METHODS: We evaluated characteristics of 435 students at Mayo Medical School (MMS) who matriculated 2000-2009 and for whom undergraduate grade point average, medical college aptitude test (MCAT), medical school standardized tests (United States Medical Licensing Examination [USMLE] 1 and 2; National Board of Medical Examiners [NBME] subject examination), and faculty assessments were available. We assessed the correlation between scores and assessments and determined USMLE 1 cutoffs predictive of poor performance (≤10th percentile) on the NBME examinations. We also compared the mean faculty assessment scores of MMS students vs visiting students, and for the NBME, we determined the percentage of MMS students who scored at or below the tenth percentile of first-time national examinees. RESULTS: MCAT scores correlated robustly with USMLE 1 and 2, and USMLE 1 and 2 independently predicted NBME scores in all clerkships. USMLE 1 cutoffs corresponding to poor NBME performance ranged from 220 to 223. USMLE 1 scores were similar among MMS and visiting students. For most academic years and clerkships, NBME scores were similar for MMS students vs all first-time examinees. CONCLUSIONS: MCAT, USMLE 1 and 2, and subsequent clinical performance parameters were correlated with NBME scores across all core clerkships. Even more interestingly, faculty assessments correlated with NBME scores, affirming patient care as examination preparation. USMLE 1 scores identified students at risk of poor performance on NBME subject examinations, facilitating and supporting implementation of remediation before the clinical years. MMS students were representative of medical students across the nation.

Progesterone support for frozen embryo transfer: intramuscular versus vaginal suppository demonstrates no difference in a cohort.

OBJECTIVE: To evaluate pregnancy rates based on the route of progesterone replacement in frozen embryo transfer (FET) cycles. STUDY DESIGN: A randomized controlled trial and retrospective analysis. In the randomized group 76 FET cycles were randomized. In the retrospective group 508 FET cycles were reviewed. Intramuscular (IM) proges-erone in oil 100 mg daily or oral micronized progesterone prior to transfer followed by compounded vaginal proges-erone 200 mg 3 times daily (OV). The main outcome measure was the clinical pregnancy rate (CPR). RESULTS: Baseline characteristics did not vary be-ween groups in either cohort. In the randomized group there were no significant differences in CPR (31.43% vs. 21.05%) or live birth rate (LBR) (31.43% vs. 18.92%) for IM and OV progesterone replacement, respectively. In the retrospective cohort patients there wore also no significant differences in CPR (35.56% vs. 32.35%) or LBR (32.23% vs. 28.51%)f or the IM and OVp rogester-ne replacement groups, respectively. CONCLUSION: This study demonstrates that either OV or IM progesterone is effective for luteal phase support for FETs.

Approach to the management of rare clinical presentations of macroprolactinomas in reproductive-aged women.

OBJECTIVE: To describe 2 cases of macroprolactinomas with atypical presentation in women desiring pregnancy that illustrate important considerations in the management approach for macroprolactinomas in reproductive-aged women. PATIENTS: Case 1 was a 26-year-old woman referred to our institution for possible tumor resection after pituitary apoplexy during her first pregnancy. Instead, she underwent treatment with cabergoline for a year with goals of normalization of prolactin and decrease in tumor size to <1 cm before trying to conceive. Case 2 was an 18-year-old woman with a macroprolactinoma intolerant to dopamine agonists. She underwent stereotactic radiosurgery, with marked reduction in tumor size and normalization of prolactin levels. She conceived and delivered a healthy infant 3 years after radiosurgery. CONCLUSION: Management of macroprolactinomas in women desiring pregnancy requires careful consideration of alternatives to surgery which could impair pituitary function and fertility and awareness of treatment goals that can minimize the risks for pituitary apoplexy and vision loss during pregnancy. It is important to increase awareness of these options prior to initiation of treatment and conception.

Unilateral oophorectomy results in compensatory follicular recruitment in the remaining ovary at time of ovarian stimulation for in vitro fertilization.

OBJECTIVE: To assess the effect of unilateral oophorectomy (UO) by assessing ovarian reserve (OVR) and the response to gonadotropin stimulation in women with UO undergoing in vitro fertilization (IVF) compared with the response of the ipsilateral ovary of women without UO. DESIGN: Historical cohort study. SETTING: Academic fertility clinic. PATIENT(S): Fifty-one women with single ovary compared with a referent group with both ovaries in a 1:2 fashion. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Day-3 follicle-stimulating hormone (FSH), estradiol, and antral follicle counts as measures of OVR, and IVF outcomes including number of follicles aspirated and oocytes retrieved. RESULT(S): The baseline demographics and serum markers of OVR were not different. Referent women had greater follicular yield and oocyte numbers when compared with women with UO; however, when compared with the ipsilateral ovary of the referents, women with UO had a higher antral follicle count and greater follicle and oocyte numbers. In multivariate analyses, the ovary from women with UO was more likely to yield more than the median number of follicles and oocytes than the ipsilateral ovary in referent women. Live-birth rates in both groups were similar. CONCLUSION(S): Our results suggest that the remaining ovary appears to compensate in follicular yield after UO in women, confirming the animal data. Women with UO can be reassured and appropriately counseled regarding IVF.

Maternal and neonatal complications of elective early-term deliveries.

Approximately 10% to 15% of all deliveries in the United States are performed before 39 completed weeks of gestation without a true medical indication for early delivery, despite long-standing recommendations against this practice. Early-term deliveries are those that occur between 3707 and 3867 weeks. It is now recognized that maternal and neonatal complications have increased for deliveries that occur at early- vs late-term gestation. The reasons for the increase in the rate of elective early-term deliveries are unclear but likely involve both patient and physician factors. Various strategies have been used to increase awareness of the morbidities associated with the practice of elective early-term delivery and to reduce its frequency. Insurers and quality accrediting agencies are increasingly holding hospitals accountable for their rates of elective early-term deliveries, and this pressure will likely continue to lead to widespread change in the practice of obstetrics. The interventions to increase adherence to evidence-based medicine guidelines that are described within this review may also be applicable to other areas of medicine.

Fertility drug use and the risk of ovarian tumors in infertile women: a case-control study.

OBJECTIVE: To assess the influence of infertility and fertility drugs on risk of ovarian tumors. DESIGN: Case-control study (Mayo Clinic Ovarian Cancer Study). SETTING: Ongoing academic study of ovarian cancer. PATIENT(S): A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. RESULT(S): Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. CONCLUSION(S): We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation.

Magnetic resonance-guided focused ultrasound surgery for leiomyoma-associated infertility.

OBJECTIVE: To describe magnetic resonance-guided focused ultrasound surgery (FUS) as a treatment for a case of leiomyoma-associated infertility. DESIGN: Case report from a randomized clinical trial. SETTING: Academic medical center. PATIENT(S): A 37-year-old woman with known leiomyomas and a history of 18 months of home-inseminations from a known donor. INTERVENTION(S): Magnetic resonance-guided FUS treatment of uterine fibroids, where the dominant fibroid distorted the uterine cavity. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): A viable intrauterine pregnancy, with a full-term vaginal delivery, was conceived after a single clomiphene citrate and intrauterine insemination cycle. CONCLUSION(S): The role of FUS for enhancement of fertility in women with nonhysteroscopically resectable uterine fibroids distorting the uterine cavity should be investigated further.

Challenges in the gynecologic care of premenopausal women with breast cancer.

Premenopausal women with a new diagnosis of breast cancer are faced with many challenges. Providing health care for issues such as gynecologic comorbidities, reproductive health concerns, and vasomotor symptom control can be complicated because of the risks of hormone treatments and the adverse effects of adjuvant therapies. It is paramount that health care professionals understand and be knowledgeable about hormonal and nonhormonal treatments and their pharmacological parameters so they can offer appropriate care to women who have breast cancer, with the goal of improving quality of life. Articles for this review were identified by searching the PubMed database with no date limitations. The following search terms were used: abnormal uterine bleeding, physiologic sex steroids, endometrial ablation, hysteroscopic sterilization, fertility preservation in endometrial cancer, tranexamic acid and breast cancer, menorrhagia treatment and breast cancer, abnormal uterine bleeding and premenopausal breast cancer, levonorgestrel IUD and breast cancer, tamoxifen and gynecologic abnormalities, tamoxifen metabolism, hormones and breast cancer risk, contraception and breast cancer, pregnancy and breast cancer, and breast cancer and infertility treatment.

Fertility preservation.

Of the estimated 1.5 million men and women who were diagnosed as having cancer in 2010, approximately 10% are younger than 45 years. For these individuals, cancer treatment can be lifesaving but can permanently affect reproductive capacity. The American Society of Clinical Oncology has recommended that oncologists discuss the possibility of infertility with reproductive-age cancer patients and offer referral for fertility preservation consultation and therapy. Fertility preservation is an emerging field that offers treatment aimed at protecting future reproductive ability for individuals with cancer or other serious illnesses. Although fertility preservation strategies vary by patient age and sex, many allow patients to store gametes or reproductive tissues for potential future use to create offspring. As an emerging discipline, many questions remain about the role of fertility preservation. We performed a MEDLINE search from 1950 to June 2010 using the following MeSH terms: amenorrhea; antineoplastic agents; ovarian failure; premature; infertility, female; fertility preservation; infertility, male; adolescent and cancer; child and cancer; cryopreservation; and reproductive technologies, assisted. Studies considered for inclusion included those written in English and published before June 2010.

Evolving spectrum: the pathogenesis of endometriosis.

Although the exact etiology of endometriosis is unknown, several hypotheses about its origin exist. Of these, Sampson's theory of retrograde menstruation is the most widely accepted. Multiple in-vitro and in vivo models have been developed to study endometriosis. Several key steps are required to establish an endometriotic implant: presence of ectopic endometrial glands and stroma, attachment of endometrial cells to the peritoneum, invasion into the mesothelium, and survival and growth of the ectopic tissue. Many of these steps are similar to those associated with neoplasia, and numerous biologic pathways are involved. It is likely that both intrinsic factors within the ectopic endometrium and permissive alterations within the host are important to the development of endometriosis.

A potential role for colony-stimulating factor 1 in the genesis of the early endometriotic lesion.

OBJECTIVE: To investigate the role(s) of colony-stimulating factor 1 (CSF-1) on the development of early endometriosis in a murine model by comparing rate of lesion formation in mice [1] homozygous for a CSF-1 mutation versus syngeneic controls and [2] after treatment with imatinib, a commercially available tyrosine kinase inhibitor that alters interaction(s) between CSF-1 and its receptor, c-fms. DESIGN: Prospective, placebo-controlled animal study. SETTING: Academic medical center. ANIMALS: Six- to 8-week old female FVB, wild-type C57BL/6, and CSF-1 op/op mice. INTERVENTION(S): Endometrial tissue from donor mice was used to induce endometriosis in murine recipients. In some experiments, mice homozygous for a CSF-1 mutation (CSF-1 op/op) were donors or recipients. In other experiments, donor and/or recipient mice received imatinib. MAIN OUTCOME MEASURE(S): Histologic confirmation of endometriosis, rate of lesion formation. RESULT(S): By 40 hours, recipient mice developed a mean of 7.2 +/- 0.9 endometriotic lesions that had invaded host surfaces, and mesothelial cells had proliferated over the entire surface of the implants. The CSF-1 op/op mice developed significantly fewer (mean 0.9 +/- 0.3) endometriotic lesions versus syngeneic controls. Imatinib treatment resulted in significantly fewer lesions when compared with sham-treated controls. CONCLUSION(S): Colony-stimulating factor 1 has a role in establishing early endometriotic lesions. Agents targeting CSF-1 or its actions have therapeutic potential for treating endometriosis.

Gamma interferon inhibits production of Anti-OspA borreliacidal antibody in vitro.

The ability of a Lyme borreliosis vaccine to induce and maintain sustained levels of borreliacidal antibody is necessary for prolonged protection against infection with Borrelia burgdorferi. Vaccination against infection with B. burgdorferi could be improved by determining the mechanism(s) that influences the production of protective borreliacidal antibody. Borreliacidal antibody was inhibited in cultures of lymph node cells obtained from C3H/HeJ mice vaccinated with formalin-inactivated B. burgdorferi and cultured with macrophages and B. burgdorferi and treated with recombinant gamma interferon (rIFN-gamma). The suppression of production of outer surface protein A (OspA) borreliacidal antibody by rIFN-gamma was not affected by the time of treatment. In addition, treatment with rIFN-gamma inhibited the production of other anti-B. burgdorferi antibodies. By contrast, treatment of cultures of immune lymph node cells with anti-IFN-gamma marginally increased the production of borreliacidal antibody and enhanced the production of other antibodies directed against B. burgdorferi. These results show that IFN-gamma does not play a major role in the production of anti-OspA borreliacidal antibody. Additional studies are needed to determine which cytokine(s) will enhance production of borreliacidal antibody.