Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Disparities in fertility preservation use among adolescent and young adult women with cancer.

PURPOSE: Women face multiple barriers to fertility preservation after cancer diagnosis, but few studies have examined disparities in use of these services. METHODS: Women aged 15-39 years diagnosed with cancer during 2004-2015 were identified from the North Carolina Central Cancer Registry and linked to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Women who cryopreserved oocytes or embryos for fertility preservation (n = 96) were compared to women who received gonadotoxic treatment but did not use fertility preservation (n = 7964). Conditional logistic and log-binomial regression were used to estimate odds ratios (ORs) or prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Few adolescent and young adult women with cancer in our study (1.2%) used fertility preservation. In multivariable regression, women less likely to use fertility preservation were older at diagnosis (ages 25-29 vs. 35-39: OR = 6.27, 95% CI: 3.35, 11.73); non-Hispanic Black (vs. non-Hispanic White: PR = 0.44, 95% CI: 0.24, 0.79); and parous at diagnosis (vs. nulliparous: PR = 0.24, 95% CI: 0.13, 0.45); or lived in census tracts that were non-urban (vs. urban: PR = 0.12, 95% CI: 0.04, 0.37) or of lower socioeconomic status (quintiles 1-3 vs. quintiles 4 and 5: PR = 0.39, 95% CI: 0.25, 0.61). CONCLUSIONS: Women with cancer who were older, non-Hispanic Black, parous, or living in areas that were non-urban or of lower socioeconomic position were less likely to use fertility preservation. IMPLICATIONS FOR CANCER SURVIVORS: Clinical and policy interventions are needed to ensure equitable access to fertility services among women facing cancer treatment-related infertility.

Patient-Reported Sexual Function Among Young Adult Cancer Survivors.

Purpose: Reproductive health and sexual function are important to survivors of Adolescent and Young adult (AYA) cancers. We evaluated the prevalence of sexual dysfunction and factors associated with dysfunction using the Patient-Reported Outcomes Measurement Information System (PROMIS) sexual function (SexFS) measure in AYAs (15-39 years old at diagnosis) enrolled in a cancer survivorship cohort. Materials and Methods: Using a cross-sectional survey of a tertiary medical center-based cancer survivorship cohort, we determined the mean PROMIS SexFS v1.0 T-scores and prevalence of scores that were indicative of dysfunction (>1/2 standard deviation [SD] below reference population mean). Multivariable generalized linear regression was performed to identify factors associated with lower scores. Results: We identified 284 AYA cancer survivors, most of whom were women (70%). The mean age at survey was 36.0 years (SD = 7.9). Overall, 31% of females and 19% of men had clinically significantly lower scores than the general U.S. population in the domain of interest, and 13% of women and 6% of men had abnormal scores for satisfaction. Twenty-six percent of male AYAs reported erectile dysfunction. The rate of sexual inactivity in the last 30 days was 27%. Low levels of physical activity were associated with lower PROMIS scores for interest in sexual activity in both men and women, and for global satisfaction with sex life in women only. Conclusions: Our results suggest that low interest in sexual activity is common among survivors of AYA cancers. Low levels of physical activity may be associated with lower levels of interest in and satisfaction with sexual activity in this population.

Pregnancy attempts among adolescent and young adult cancer survivors.

OBJECTIVE: To examine whether demographic and cancer-related characteristics and factors such as fertility discussion with a medical provider and fertility preservation use are associated with attempting pregnancy after adolescent and young adult cancer. DESIGN: Cross-sectional online survey. SETTING: Not applicable. PATIENT(S): Women with lymphoma, breast cancer, thyroid cancer, or gynecologic cancer diagnosed at 15-39 years from 2004 to 2016 were identified from the North Carolina Cancer Registry and the Kaiser Permanente Northern and Southern California health care systems and responded to an online survey addressing survivorship concerns, including fertility and reproductive outcomes. EXPOSURES: Demographic characteristics, cancer characteristics, fertility discussion with a medical provider or fertility specialist between cancer diagnosis and starting cancer treatment, use of fertility preservation strategies (freezing embryos or oocytes) after cancer diagnosis. MAIN OUTCOME MEASURE(S): Pregnancy attempt after cancer diagnosis, defined by either a pregnancy or 12 months of trying to become pregnant without pregnancy. RESULT(S): Among 801 participants who had not reached their desired family size at diagnosis, 77% had a fertility discussion with any medical provider between cancer diagnosis and treatment initiation, and 8% used fertility preservation after cancer diagnosis. At survey (median =7 years after diagnosis; interquartile range, 4-10), 32% had attempted pregnancy. Neither fertility discussion with any medical provider nor fertility counseling with a fertility specialist was significantly associated with pregnancy attempts. However, the use of fertility preservation was significantly associated with attempting pregnancy (prevalence ratios = 1.74; 95% confidence interval: 1.31-2.32). Other characteristics positively associated with pregnancy attempts included younger age at diagnosis, longer time since diagnosis, having a partner (at diagnosis or at survey), and having a history of infertility before cancer diagnosis. CONCLUSION(S): Use of fertility preservation strategies was uncommon in our cohort but was associated with attempting pregnancy after cancer. Ensuring access to fertility preservation methods may help adolescent and young adult cancer survivors to plan and initiate future fertility.

Time to cancer treatment and reproductive outcomes after fertility preservation among adolescent and young adult women with cancer.

BACKGROUND: Fertility preservation (FP) may be underused after cancer diagnosis because of uncertainty around delays to cancer treatment and subsequent reproductive success. METHODS: Women aged 15 to 39 years diagnosed with cancer between 2004 and 2015 were identified from the North Carolina Central Cancer Registry. Use of assisted reproductive technology (ART) after cancer diagnosis between 2004 and 2018 (including FP) was assessed through linkage to the Society for Assisted Reproductive Technology. Linear regression was used to examine time to cancer treatment among women who did (n = 95) or did not (n = 469) use FP. Modified Poisson regression was used to estimate risk ratios (RRs) and 95% CIs for pregnancy and birth based on timing of ART initiation relative to cancer treatment (n = 18 initiated before treatment for FP vs n = 26 initiated after treatment without FP). RESULTS: The median time to cancer treatment was 9 to 33 days longer among women who used FP compared with women who did not, matched on clinical factors. Women who initiated ART before cancer treatment may be more likely to have a live birth given pregnancy compared with women who initiated ART after cancer treatment (age-adjusted RR, 1.47; 95% CI, 0.98-2.23), though this may be affected by the more frequent use of gestational carriers in the former group (47% vs 20% of transfer cycles, respectively). CONCLUSIONS: FP delayed gonadotoxic cancer treatment by up to 4.5 weeks, a delay that would not be expected to alter prognosis for many women. Further study of the use of gestational carriers in cancer populations is warranted to better understand its effect on reproductive outcomes.

Fertility Preservation and Financial Hardship among Adolescent and Young Adult Women with Cancer.

BACKGROUND: Financial hardship among adolescents and young adults (AYA) with cancer who receive gonadotoxic treatments may be exacerbated by the use of fertility services. This study examined whether AYA women with cancer who used fertility preservation had increased financial hardship. METHODS: AYA women with cancer in North Carolina and California completed a survey in 2018-2019. Cancer-related financial hardship was compared between women who cryopreserved oocytes or embryos for fertility preservation after cancer diagnosis (n = 65) and women who received gonadotoxic treatment and reported discussing fertility with their provider, but did not use fertility preservation (n = 491). Multivariable log-binomial regression was used to estimate prevalence ratios and 95% confidence intervals (CI). RESULTS: Women were a median age of 33 years at diagnosis and 7 years from diagnosis at the time of survey. Women who used fertility preservation were primarily ages 25 to 34 years at diagnosis (65%), non-Hispanic White (72%), and had at least a Bachelor's degree (85%). In adjusted analysis, use of fertility preservation was associated with 1.50 times the prevalence of material financial hardship (95% CI: 1.08-2.09). The magnitude of hardship was also substantially higher among women who used fertility preservation: 12% reported debt of ≥$25,000 versus 5% in the referent group. CONCLUSIONS: This study provides new evidence that cryopreserving oocytes or embryos after cancer diagnosis for future family building is associated with increased financial vulnerability. IMPACT: More legislation that mandates insurance coverage to mitigate hardships stemming from iatrogenic infertility could improve access to fertility preservation for young women with cancer.

Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial.

BACKGROUND: Women with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth. METHODS AND FINDINGS: In this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m2) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (-6.6 ± 5.4% versus -0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful. CONCLUSIONS: A preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02432209.

Embryo re-expansion does not affect clinical pregnancy rates in frozen embryo transfer cycles: a retrospective study.

PURPOSE: A retrospective study examining the effects of embryo re-expansion before transfer on pregnancy outcomes for frozen embryo transfers (FET). METHODS: A total of 486 FET cycles from November 2017 through December 2019 were studied. These cycles included patients using autologous, donor oocytes, and donor embryo with patients ranging from ages 23 to 48 years with infertility diagnoses. Programmed FET priming was performed with exogenous estrogen and progesterone. All blastocysts were cultured in trigas incubators for 20 min to 4 h and 42 min. Pictures of each blastocyst after thaw and before transfer were taken utilizing the Hamilton Thorne Zilos laser software (Beverly, MA). The longest portion of the embryo was measured in µm. Pregnancy was defined by a positive hCG, and ongoing clinical pregnancy was defined by the presence of fetal cardiac activity. Wilcoxon rank sum tests were used to access differences in change parameters. RESULTS: There is no significant difference in the amount of embryo expansion or contraction to achieve an ongoing pregnancy. The difference remained non-significant when stratified by embryo expansion or contraction. The amount of change over time and percent change from the first measurement were also not associated with achieving an ongoing pregnancy. This remained true after adjustment for patient age and whether or not a biopsy was performed. CONCLUSIONS: Embryos that do not re-expand after warming appear to have a similar chance of achieving a successful pregnancy as those that do re-expand.

Sperm morphology from the actual inseminated sample does not predict clinical pregnancy following intrauterine insemination.

OBJECTIVE: To determine the effect of sperm morphology from the specific sample used for intrauterine insemination (IUI) on clinical pregnancy rates (CPR). DESIGN: Prospective cohort study. SETTING: Academic fertility clinic. PATIENTS: Couples undergoing IUI July 2016-January 2017. INTERVENTIONS: Morphology slides were prepared from the semen sample produced for IUI. MAIN OUTCOME MEASURES: CPR was measured by detection of cardiac activity. Multiple logistic regression modeling was performed to determine the association of sperm morphology with CPR, controlling for age, antimüllerian hormone level, and post-wash total motile sperm count. RESULTS: Semen analyses, including Kruger strict criteria for morphology from the actual sample inseminated, were reviewed for 155 couples, comprising 234 total treatment cycles. The percent normal morphology significantly differed between the preliminary semen analysis and the IUI sample (-2.0% +3.7% (95% CI -2.55, -1.53). Of the total 234 treatment cycles, 8.6% resulted in clinical pregnancy. When categorized by strict morphology >4%, <4%, and <1%, the CPR was 6.6%, 9.8%, and 10.9%, respectively. In couples with otherwise normal semen parameters (isolated teratospermia), CPR by >4%, <4%, and <1% normal forms was 7.2%, 9.8%, and 11.1%, respectively. There was no significant association between the percent normal morphology and CPR in multivariate analysis. CONCLUSIONS: This study evaluating the morphology of the actual inseminated sample did not find differences in CPR following IUI among couples with normal and abnormal sperm morphology, including severe teratospermia. Abnormal sperm morphology should not exclude couples from attempting IUI.

The Adolescent and Young Adult (AYA) Horizon Study: An AYA Cancer Survivorship Cohort.

BACKGROUND: In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States. METHODS: The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15-39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data. RESULTS: We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall (N = 1,679), and notably lower among minority groups compared with non-Hispanic white women. CONCLUSIONS: Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements. IMPACT: The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care.

Time to blastulation is superior to individual components of embryo grading for live-birth prediction.

OBJECTIVE: To compare components of the embryo grading system with time for blastocyst formation (i.e., day of embryo transfer) for predicting live-birth rate in frozen embryo transfer cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility clinic. PATIENTS: From January 2015 to October 2018, 870 frozen embryos transferred in a total of 509 women and 728 cycles at our institution. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Probability of live birth per cycle. RESULTS: In unadjusted analysis of embryo grading components, both inner cell mass (ICM) and trophectoderm grades demonstrated a correlation with live-birth rates. However, this effect was lost in the ICM subgroup analysis by day of embryo transfer and preserved only in declining trophectoderm grades of day-6 transfers. In the adjusted analysis for prediction of live birth, only day of transfer was statistically significant. When assessing the composite score by Society for Assisted Reproductive Technology (SART) embryo grading, good embryos that blastulated on day 6 were statistically significantly less likely than day-5 embryos to result in live birth (risk ratio 0.70; 95% confidence interval, 0.58-0.85). Finally, in a predictive model adjusted for all individual components of embryo grade, the day of blastulation was the only statistically significant contributor. CONCLUSIONS: Time to blastulation is superior to other individual components of embryonic grading for prediction of live birth.

Does empiric superovulation improve fecundity in healthy women undergoing therapeutic donor insemination without a male partner?

OBJECTIVE: To evaluate whether superovulation improves fecundity in women undergoing therapeutic donor insemination (TDI). DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility clinic. PATIENT(S): Healthy women aged 23-45 years with no history of or risk factors for infertility who underwent 152 medicated and 104 unmedicated TDI cycles from 2013 to 2018. INTERVENTION: Unmedicated TDI versus use of medication in a TDI cycle (clomiphene citrate or letrozole). MAIN OUTCOME MEASURE(S): Cumulative probability of pregnancy in six TDI cycles. RESULT(S): In adjusted all-cycle analysis, medicated TDI cycles were less likely to result in pregnancy compared with unmedicated cycles. The incidence of twins was 23% in the medicated group and 0% in the unmedicated group. Medicated cycles were less likely to result in pregnancy in women younger than 40 years or with an antimüllerian hormone (AMH) level >1.2. After three cycles not resulting in pregnancy, the only women who conceived were those who crossed over from an unmedicated to a medicated cycle (12% vs. 0%). CONCLUSION(S): Patients undergoing unmedicated TDI cycles had higher fecundity and no incidence of twin gestations. Older women, those with low AMH, and those who fail to conceive after three unmedicated cycles may benefit from medication.

Fertility-related experiences after breast cancer diagnosis in the Sister and Two Sister Studies.

BACKGROUND: Commonly used chemotherapies can be toxic to the ovaries. To the authors' knowledge, the majority of studies evaluating receipt of fertility counseling for women in their reproductive years have been performed in specific settings, thereby limiting generalizability. METHODS: A nationwide sample of US women diagnosed with breast cancer before age 45 years completed a survey assessing the prevalence of fertility counseling. Age-adjusted log-binomial regression was used to estimate prevalence ratios (PRs) and 95% CIs for fertility counseling. RESULTS: Among 432 survivors diagnosed between 2004 and 2011, 288 (67%) had not discussed the effects of treatment on fertility with a health care provider before or during treatment. Fertility discussion was associated with younger age (PR, 3.49 [95% CI, 2.66-4.58] for aged <35 years vs ≥40 years) and lower parity (PR, 1.81 [95% CI, 1.29-2.53] for parity 1 vs 2). Approximately 20% of respondents reported that they were interested in future fertility (87 of 432 respondents) at the time of their diagnosis, but not all of these individuals (66 of 87 respondents) received counseling regarding the impact of treatment on their fertility, and few (8 of 87 respondents) used fertility preservation strategies. Among 68 women with a fertility interest who provided reasons for not taking steps to preserve fertility, reasons cited included concern for an adverse impact on cancer treatment (56%), lack of knowledge (26%), decision to not have a child (24%), and cost (18%). CONCLUSIONS: Across multiple treatment settings, the majority of women of reproductive age who are diagnosed with breast cancer did not discuss fertility with a health care provider or use fertility preservation strategies. Discussing the potential impact of cancer treatment on future fertility is an important aspect of patient education.

Applying behavioral theory to understand fertility consultation uptake after cancer.

OBJECTIVE: The objective of this study was to examine the association between theoretical constructs from the Health Belief Model and fertility consultation status after cancer. METHODS: Reproductive-aged female cancer survivors self-reported their use of fertility consultation, perceived severity of and susceptibility to infertility, perceived barriers to and effectiveness of fertility consultation, and cues to action from family/peers and doctors, as well as demographics and cancer characteristics. Logistic regression was used to analyze the association between theoretical constructs and fertility consultation status. RESULTS: Fertility consultation uptake was more prevalent among survivors with higher incomes, those without children, those who wanted a (another) child, and those who were diagnosed more recently. In the final multivariate model, higher perceived severity of infertility, fewer perceived barriers to fertility consultation, and more cues to action from family/peers and doctors were significantly associated with fertility consultation uptake, controlling for income. Exploratory bivariate analyses of barriers to fertility consultation revealed that cost and trouble accessing services were significantly associated with not having a fertility consultation. CONCLUSIONS: The Health Belief Model is useful for understanding factors associated with fertility consultation uptake. Efforts should be made to reduce financial barriers and improve patient-centered assessment of family-building goals.

MULTIPLE PITUITARY ADENOMAS WITH FUNCTIONAL FOLLICLE-STIMULATING HORMONE SECRETION LEADING TO OVARIAN HYPERSTIMULATION SYNDROME.

OBJECTIVE: To present a rare case of multiple pituitary adenomas with a functional follicle-stimulating hormone component leading to ovarian hyperstimulation syndrome. METHODS: We present the clinical, laboratory, imaging, and pathologic findings along with a review of the literature. RESULTS: A 28-year-old female presented with 5 months of amenorrhea and abdominal pain. Physical exam was unremarkable. Labs revealed elevated prolactin (94 ng/mL), elevated estradiol (608 pg/mL), inappropriately normal follicle-stimulating hormone (10.2 mIU/mL), and suppressed luteinizing hormone (0.36 mIU/mL). Transvaginal ultrasound showed numerous large ovarian cysts bilaterally. Brain magnetic resonance imaging showed a 1.2-cm sellar mass. Various medical therapies were not tolerated due to side effects and the patient underwent gross total resection of the sellar mass with marked improvement in her symptoms and blood hormone levels, resumption of menstruation, and shrinkage of the ovarian cysts. Histologic examination revealed 3 separate staining patterns consistent with multiple pituitary adenomas. CONCLUSION: Functioning gonadotroph adenomas are rare and often difficult to diagnose, though in premenopausal women they can lead to the distinct clinical presentation of spontaneous ovarian hyperstimulation syndrome. The favored treatment approach is surgical as it has the highest reported success rate. Recurrence is not uncommon and long-term surveillance is recommended. Given limited data on long-term follow-up, the role of available therapies is not well defined, and further research is needed. To our knowledge, this is the first reported case of multiple pituitary adenomas that included a functional gonadotroph component.

Suspected Testosterone-Producing Tumor in a Patient Taking Biotin Supplements.

A perimenopausal woman presented with palpitations, hirsutism, and inability to lose weight. Laboratory tests revealed an unusual endocrine hormonal profile including pituitary hormones (TSH, ACTH, and prolactin) below reference intervals and gonadal (testosterone) and adrenal (cortisol) hormones above reference intervals. Ultimately, after a comprehensive workup including a scheduled surgical procedure, abnormal laboratories were determined due to biotin interference. Biotin (vitamin B7) is a water-soluble vitamin and essential cofactor for the metabolism of fatty acids, glucose, and amino acids. The recommended daily intake of biotin for adults is 30 µg/d. Many over-the-counter products, particularly those marketed for hair, skin, and nail growth, contain biotin 100-fold of recommended daily intake. This case is unique due to the abnormalities observed not only in the well-described TSH "sandwich" immunoassay, but also in tests for gonadal steroids, adrenal, and pituitary hormones. Falsely high as well as falsely low results can be ascribed to biotin. Competitive immunoassays (Fig. 1A)- in this case, tests used initially for serum cortisol and testosterone- can demonstrate falsely high results. Interference falsely lowers the immunometric "sandwich" immunoassay (Fig. 1B)-in this case, TSH. Biotin effect on our patient's endocrine testing led to decidedly abnormal findings, unnecessary medical referrals and diagnostic studies, and comprehensible psychological distress. Interference with one immunoassay, TSH, persisted a full 2 weeks after discontinuation of biotin; indeed, some tests demonstrate sensitivity to lesser quantities of biotin. Improved communication between patients, health care providers, and laboratory professionals is required concerning the likelihood of biotin interference with immunoassays.

Childbirth after adolescent and young adult cancer: a population-based study.

PURPOSE: Annually, > 45,000 US women are diagnosed with cancer during adolescence and young adulthood (AYA). Since 2006, national guidelines have recommended fertility counseling for cancer patients. We examined childbirth after AYA cancer by calendar period, cancer diagnosis, and maternal characteristics. METHODS: We identified a cohort of women with an incident invasive AYA cancer diagnosis at ages 15-39 during 2000-2013 in North Carolina. Cancer records were linked with statewide birth certificates through 2014. Hazard ratios (HR) and 95% confidence intervals (CI) for first post-diagnosis live birth were calculated using Cox proportional hazards regression. RESULTS: Among 17,564 AYA cancer survivors, 1989 had ≥ 1 birth after diagnosis during 98,397 person-years. The 5- and 10-year cumulative incidence of live birth after cancer was 10 and 15%, respectively. AYA survivors with a post-diagnosis birth were younger at diagnosis, had lower stage disease, and had less often received chemotherapy than those without a birth. The 5-year cumulative incidence of post-diagnosis birth was 10.0% for women diagnosed during 2007-2012, compared to 9.4% during 2000-2005 (HR = 1.01; 0.91, 1.12), corresponding to periods before and after publication of American Society of Clinical Oncology fertility counseling guidelines in 2006. CONCLUSIONS: Despite advances in fertility preservation options and recognition of fertility counseling as a part of high-quality cancer care, the incidence of post-diagnosis childbirth has remained stable over the last 15 years. IMPLICATIONS FOR CANCER SURVIVORS: Our study uses statewide data to provide recent, population-based estimates of how often AYA women have biological children after a cancer diagnosis.

Cycle day, estrogen level, and lead follicle size: analysis of 27,790 in vitro fertilization cycles to determine optimal start criteria for gonadotropin-releasing hormone antagonist.

OBJECTIVE: To determine the optimal criteria at which to start GnRH antagonists during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: Retrospective clinical cohort. SETTING: IVF clinics. PATIENT(S): Women undergoing fresh autologous IVF using GnRH antagonist for ovulation suppression during COH. INTERVENTION(S): Measurement of lead follicle size, E2 level, and cycle day of stimulation on day of antagonist initiation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR). RESULT(S): The highest clinical PR was achieved when the antagonist was started when a lead follicle reached 14-15.9 mm in size (mean clinical PR 21.3; 95% confidence interval [CI] 19.3, 23.6) on cycle day 6 (mean clinical PR 22.2; 95% CI 17, 28.4), or when the E2 level was between 500 and 599 pg/mL (mean clinical PR 25.4; 95% CI 19.5, 32.4). Starting antagonists when the E2 level was <300 or >1,100 pg/mL reduced the odds of clinical pregnancy by 40% (odds ratio 0.60, 95% CI 0.5, 0.7). CONCLUSION(S): Cycle day, E2 level, and follicle size at time of antagonist start are all independent predictors of a clinical pregnancy after IVF. Initiating antagonists when the E2 level is extremely low (<300 pg/mL) or extremely high (>1,100 pg/mL) significantly reduces the odds of pregnancy.

Acute Menopausal Symptoms in Young Cancer Survivors Immediately following Chemotherapy.

PURPOSE: The aim of this study was to evaluate the prevalence of menopausal symptoms in young cancer survivors immediately following the completion of chemotherapy. METHODS: This prospective cohort study followed 124 young females with a new diagnosis of cancer requiring chemotherapy to assess symptoms of menopause before treatment and immediately following chemotherapy. Symptoms were compared before and after treatment using the McNemar test and between cancer patients and 133 similar-aged healthy controls using Pearson χ2 and Fisher's exact tests. RESULTS: Participants undergoing cancer therapy reported more menopausal symptoms compared to controls prior to the initiation of any treatment (hot flashes or night sweats 33 vs. 7%, p < 0.01, trouble sleeping 57 vs. 31%, p < 0.01, headaches 50 vs. 35%, p = 0.02, and decreased libido 36 vs. 16%, p < 0.01) and also reported a greater prevalence of symptoms immediately after cancer therapy compared to pretreatment prevalence (vasomotor symptoms, p < 0.01, vaginal dryness, p < 0.01, decreased concentration, p < 0.01, and body aches, p = 0.01). Cancer patients with lower anti-Müllerian hormone (AMH) levels after treatment (<0.10 ng/mL) had an increased risk of vasomotor symptoms (OR 2.2, p = 0.04), mood swings (OR 2.4, p = 0.03), feeling sad (OR 2.2, p = 0.04), trouble sleeping (OR 2.7, p = 0.02), and decreased libido (OR 3.0, p = 0.03) when controlled for age and cancer type, and the incidence of these symptoms was not affected by the use of systemic hormones or psychiatric medications. Treatment length, use of alkylating agents, pelvic radiation, and marital status were also not associated with the prevalence of menopausal symptoms. CONCLUSIONS: Premenopausal women with a new cancer diagnosis have more menopausal symptoms than females of similar age before and after cancer treatment, the effects of which are not mitigated by systemic hormone use. Decreased AMH levels were associated with an increased likelihood of reporting physiologic symptoms after therapy. IMPLICATIONS FOR CANCER SURVIVORS: This information is imperative for counseling; ultimately, improved symptom management during and after cancer therapies will improve quality of life in young cancer survivors.