Fertility preservation in patients undergoing gonadotoxic treatments: a Canadian Fertility and Andrology Society clinical practice guideline.

The management of young patients with cancer presents several unique challenges. In general, these patients are ill prepared for the diagnosis and the impact on their fertility. With the improved survival for all tumour types and stages, the need for adequate fertility counselling and a multidisciplinary approach in the reproductive care of these patients is paramount. Recent advances in cryopreservation techniques allow for the banking of spermatozoa, oocytes, embryos and ovarian tissue without compromising survival. This Canadian Fertility and Andrology Society (CFAS) guideline outlines the current understanding of social and medical issues associated with oncofertility, and the medical and surgical technologies available to optimize future fertility.

Reproductive late effects after hematopoietic stem cell transplant in pediatric, adolescent, and young adult cancer survivors.

Reproductive late effects after hematopoietic stem cell transplant can have a significant impact on cancer survivors' quality of life. Potential late effects include gonadal insufficiency, genital graft-versus-host disease, uterine injury, psychosexual dysfunction, and an increased risk of breast and cervical cancer in patients treated with total body irradiation. Despite guidelines, screening and treatment are not standardized among at-risk patients. Provider barriers include lack of knowledge of at-risk therapies and evidenced-based guidelines. Patient barriers include a reluctance to report symptoms and lack of awareness of treatment options. System barriers include inefficient implementation of screening tools and poor dissemination of guidelines to providers who serve as the medical home for survivors. This review guides the clinician in identifying and managing reproductive late effects after hematopoietic stem cell transplant to improve outcomes.

Female reproductive health in pediatric, adolescent, and young adult cancer survivors.

An estimated 500,000 cancer survivors of reproductive age in the United States will live to experience the long-term consequences of cancer treatment. Therefore, a focused aspect of cancer care has appropriately shifted to include quality of life in survivorship. Infertility is a late effect of therapy that affects 12% of female survivors of childhood cancer receiving any cancer treatment in large cohort studies and results in a 40% decreased likelihood of pregnancy in young adults of ages 18-39 years. Nonfertility gynecologic late effects such as hypoestrogenism, radiation-induced uterine and vaginal injury, genital graft-versus-host disease after hematopoietic stem cell transplant, and sexual dysfunction also significantly affect quality of life in survivorship but are underdiagnosed and require consideration. Several articles in the special edition "Reproductive Health in Adolescent and Young Adult Cancer Survivorship" address infertility, genital graft-versus-host disease, and psychosexual functioning in survivorship. This review article focuses on other adverse gynecologic outcomes of cancer therapies including hypogonadism and hormone replacement therapy, radiation-induced uterovaginal injury, vaccination and contraception, breast and cervical cancer screening, and pregnancy considerations in survivorship.

Reduced-Intensity Conditioning Mitigates Risk for Primary Ovarian Insufficiency but Does Not Decrease Risk for Infertility in Pediatric and Young Adult Survivors of Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for many pediatric malignant and nonmalignant conditions. Gonadal insufficiency or infertility is present in almost all HSCT survivors who received a myeloablative conditioning (MAC) regimen. Reduced-intensity conditioning (RIC) regimens are being increasingly used in medically fragile patients or in patients with nonmalignant diagnoses to limit the toxicities associated with HSCT; however, the short-term and long-term gonadal toxicity of RIC regimens in pediatric and young adult survivors remains unknown. In this study, we compared the prevalence of gonadal insufficiency and infertility among pubertal and postpubertal pediatric and young adult survivors of HSCT who received a RIC regimen versus those who received a MAC regimen. Twenty-three females (RIC, n = 8; MAC, n = 15) and 35 males (RIC, n = 19; MAC, n = 16) were included in this single-center, retrospective cross-sectional study. Eligible patients were those with available laboratory results who were ≥1 year post-HSCT, age <40 years, and pubertal or postpubertal as assessed by an endocrinologist. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) levels were measured in females, and FSH, LH, total testosterone, and inhibin B (InhB) levels were measured in males. Twenty-one males (RIC, n = 11; MAC, n = 10) underwent semen analysis through a separate consent. Parametric and nonparametric analyses were undertaken to compare the RIC and MAC groups. Female patients who received RIC were less likely than those who received MAC to develop primary ovarian insufficiency, as demonstrated by elevated FSH (P = .02) and low estradiol (P = .01) or elevated LH (P = .09). Most females in the RIC (75%) and MAC (93%) groups had low AMH levels, indicating low or absent ovarian reserve, with no significant difference between the groups (P = .53). In males, there were no significant differences between the 2 groups in the prevalence of abnormal FSH, LH, testosterone, or InhB levels. Ten of 11 RIC males (91%) and 10 of 10 MAC males (100%) had azoospermia or oligospermia, at a median time to semen analysis from HSCT of 3.7 years (range, 1.3 to 12.2 years). RIC may pose less risk than MAC for primary ovarian insufficiency among female survivors of HSCT; however, both female and male recipients of either RIC or MAC regimens are at high risk for infertility. In the largest reported series of semen analyses of pediatric and young adult male recipients of RIC, azoospermia or oligospermia was found in nearly all (91%) RIC survivors. All patients undergoing HSCT should receive counseling about the high risk of gonadal toxicity, and efforts should be made to preserve fertility in patients undergoing either RIC or MAC.

The Impact of Macronutrient Intake on Sex Steroids During Onset of Puberty.

INTRODUCTION: Increased fiber intake has been associated with decreased breast cancer risk, while increased animal protein intake with increased risk. The objective of this study is to examine the relationship of dietary fiber and protein intake to estrogen and sex hormone-binding globulin (SHBG) concentrations at puberty onset. METHODS: These analyses were conducted using the Cincinnati puberty cohort of the Breast Cancer and the Environment Research Program, with girls followed every 6 months from ages 6 and 7. The analyses included serum measurements at 6-month intervals for estrogen and SHBG concentrations, from 18 months prior to breast stage 2 (onset of puberty). Dietary intake was documented via 24-hour dietary recalls every 3 months. Dietary factors of interest included total energy intake; total and animal protein; total, soluble, and insoluble fiber; and lignan and flavanol intake. RESULTS: This study included 260 participants who generated 871 serum specimens and 3,000 days of diet intake. In longitudinal models, estradiol was associated inversely with insoluble fiber intake; estrone positively with animal protein intake; SHBG with greater insoluble fiber and lower total protein intake; and ratio of estrone to SHBG, a measure of bioavailable estrogen, positively with animal protein. CONCLUSIONS: Greater protein intake, especially animal protein, led to greater estrogen concentrations and lower SHBG; greater animal protein and greater caloric intake led to increased bioavailable estrogen. This relationship may have served an evolutionary advantage in the past for greater fertility with adequate high-quality protein; in contemporary women, a modest decrease in animal protein may be beneficial in reducing breast cancer risk.

Suboptimal prenatal screening of Chlamydia trachomatis and Neisseria gonorrhoeae infections in a Montréal birthing and tertiary care centre: A retrospective cohort study.

BACKGROUND: The Canadian Paediatric Society no longer recommends the use of universal ocular prophylaxis with erythromycin ointment to prevent ophthalmia neonatorum. Screening for Chlamydia trachomatis and Neisseria gonorrhoeae in all pregnant women is considered the most effective way of preventing vertical transmission and ophthalmia neonatorum. OBJECTIVE: The aims of this study were to assess prenatal screening rates of C. trachomatis and N. gonorrhoeae and to compare sociodemographic factors between those screened and those not screened. METHODS: The list of all women who delivered at a tertiary care hospital in Montréal, Québec, between April 2015 and March 2016, was cross-referenced with the list of samples tested for C. trachomatis and N. gonorrhoeae. Maternal medical records were reviewed for demographic, prenatal and diagnostic information. RESULTS: Of 2,688 mothers, 2,245 women were screened at least once, but only 2,206 women had at least one valid C. trachomatis and N. gonorrhoeae result the day of delivery (82.1%; 95% CI: 80.6%-83.5%). Infection was detected in 46/2,206 (2.1%) screened women: 42 had C. trachomatis infection, two had N. gonorrhoeae infection and two were co-infected. C. trachomatis infection was more frequent in women younger than 25 years (9.8%; 95% CI: 6.7%-13.8%) than in older women (0.8%; 95% CI: 0.4%-1.3%; p<0.001). Each increase in parity decreased the probability of being tested (adjusted odds ratio=0.89; 95% CI: 0.80%-0.97%; p=0.01). Of those with an initial negative test result, 35/267 (13.1%; 95% CI: 9.3%-17.8%) of women younger than 25 years and 122/1,863 (6.6%; 95% CI: 5.5%-7.8%; p<0.001) of women aged 25 years and older were retested. Subsequent infection was detected in 4/35 (11%) women, all younger than 25. CONCLUSION: Suboptimal screening rates for C. trachomatis and N. gonorrhoeae suggest that current universal ocular prophylaxis cannot be discontinued. Repeating universal screening should be considered, especially among those younger than 25 years.

Preeclampsia: should plasma albumin level be a criterion for severity?

OBJECTIVES: To determine whether plasma albumin level (ALB) is associated with preeclampsia (PE) complications and to define its role in the evaluation of the severity of PE. METHODS: We conducted a retrospective study of women with PE at CHU Ste-Justine from January 2005 to December 2008 who had an ALB measurement before delivery. Severe PE was defined according to the Society of Obstetricans and Gynaecologists of Canada guidelines, except for the ALB and gestational age at diagnosis. We compared ALB between women with non-severe PE and with severe PE. The rates of maternal complications and adverse perinatal outcomes associated with PE were compared between women with an ALB < 20 g/L and those with an ALB ≥ 20 g/L. RESULTS: Among the 459 women included, 62.7% met the criteria for a diagnosis of severe PE. The mean gestational age was 33.8 ± 4.1 weeks at diagnosis of PE and 34.6 ± 3.9 weeks at delivery. After adjustment for gestational age and number of fetuses, ALB was found to be lower in women with severe PE (23.5 ± 3.7 vs. 25.9 ± 2.8 g/L; P < 0.05). Thrombocytopenia, increased serum ALT, severe proteinuria, and a need for platelet transfusion were more frequent among the 44 women with an ALB < 20 g/L (P < 0.05). Two women who had an ALB < 20 g/L and no other criteria for PE developed PE before 34 weeks' gestation. CONCLUSION: A plasma albumin level below 20 g/L was not found to be an independent marker for severe preeclampsia because all women with a low plasma albumin level had other adverse conditions.