The use of fertility treatments among reproductive-aged women after cancer.

OBJECTIVE: To examine whether female cancer survivors are more likely to pursue care for infertility after cancer than women without cancer. DESIGN: Population-based cohort study involving detailed interviews regarding reproductive history. SETTING: Not applicable. PATIENTS: Female cancer survivors aged 22-45 years, who were at least 2 years after a cancer diagnosis between the ages of 20 and 35 years (n = 1,036), and age-matched comparison women with no cancer history (n = 1,026). EXPOSURE: History of cancer vs. no history of cancer. MAIN OUTCOME MEASURE(S): Each cancer survivor was randomly matched to a comparison woman, who was assigned an artificial age at cancer diagnosis equal to that of her match. Matching was repeated 1,000 times. Outcomes of visiting a doctor for help becoming pregnant or undergoing fertility treatment were modeled using Cox proportional hazards regression, comparing survivors after a cancer diagnosis to age-matched comparison women, adjusted for race, income, residence, education, and parity. RESULTS: Only 25.5% of cancer survivors reported meeting their desired family size before a cancer diagnosis. The median time from diagnosis to interview among survivors was 7 (interquartile range 5-11) years. Cancer survivors were more likely to report having no children (32.6%) at the interview compared with women with no cancer history (19.5%). Survivors were not more likely to visit a doctor for help becoming pregnant compared with women without a cancer history, matched on birth year and followed by the age at which cancer survivors received their diagnosis (hazard ratio [HR] 1.16, 95% simulation interval [SI] 0.78-1.74). Compared with cancer-free women, cancer survivors had similar probabilities of pursuing any treatment (adjusted HR [aHR] 0.88, 95% SI 0.46-1.56), using hormones or medications (aHR 0.86, 95% SI 0.46-1.63), or undergoing intrauterine insemination (aHR 1.26, 95% SI 0.40-5.88) to conceive. Cancer survivors were slightly more likely to pursue surgical interventions to become pregnant (HR 1.55, 95% SI 0.67-3.71). Of those who visited a doctor but declined to pursue fertility treatment, one-quarter of women reported declining treatment due to cost. CONCLUSION: Cancer survivors did not use fertility treatments at higher rates than the general population. Further counseling and education surrounding fertility options are recommended for young adult female cancer patients after treatment is completed.

The Risk of Infertility After Surgery for Benign Ovarian Cysts.

Background: There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. However, it is unclear whether ovarian cyst surgery puts women at risk of future infertility. This study investigates whether surgery for benign ovarian cysts is associated with long-term infertility risk. Methods: Women aged 22-45 years (n = 1,537) were invited to participate in an interview about their reproductive histories, including whether they ever had infertility or ovarian cyst surgery. Each woman reporting cyst surgery was randomly matched to a comparison woman, who was assigned an artificial surgery age equal to that of her match. Matching was repeated 1,000 times. Adjusted Cox models were fit to examine time to infertility after surgery for each match. A subset of women was invited to participate in a clinic visit to assess markers of ovarian reserve (anti-Müllerian hormone [AMH], antral follicle count). Results: Approximately 6.1% of women reported cyst surgery. Infertility after surgery was more common for women reporting cyst surgery than those without surgery after adjusting for age, race, body mass index, cancer history, parity before assigned surgery age, history of infertility before surgery age, and endometriosis (median-adjusted hazard ratio 2.41, 95% simulation interval 1.03-6.78). The estimated geometric mean (95% confidence interval [CI]) AMH levels of those who reported a history of ovarian cyst surgery were 1.08 (95% CI: 0.57-2.05) times those of women who reported no history of surgery. Conclusions: Those with a history of ovarian cyst surgery were more likely to report having a history of infertility compared with age-matched women who reported no history of cyst surgery. It is possible that both ovarian surgery to remove cysts and the conditions that lead women to develop cysts requiring surgery may affect subsequent successful conception.

Potential misclassification of diabetes and prediabetes in the U.S.: Mismatched HbA1c and glucose in NHANES 2005-2016.

AIMS: To assess the prevalence and clinical implications of "mismatches" between HbA1c and glucose levels in the United States across the life course. METHODS: Participants ages 12-79 years from U.S. National Health and Nutrition Examination Survey (NHANES) 2005-2016 without known diagnosis of diabetes and who had a 75 g oral glucose tolerance test were included. Previously undiagnosed diabetes (DM), prediabetes, and normal glucose metabolism (NGM) were defined using American Diabetes Association cut-points. Mismatches were defined by the hemoglobin glycation index (HGI). RESULTS: In 10,361 participants, 5% and 41% had diabetes and prediabetes, respectively, by fasting or 2-hour glucose criteria. By HbA1c criteria, the high HGI tertile consisted of mostly abnormal classification (3% DM, 52% prediabetes) and the low HGI tertile contained mostly normal classification (78% NGM). Across all ages, 15% (weighted: 30 million individuals) had clinically significant mismatches of HGI magnitude ≥+0.5% (i.e., high mismatch) or ≤-0.5% (low mismatch). Mismatch was most common in older adults and non-Hispanic Black participants. CONCLUSIONS: Mismatches of clinically significant magnitude could lead to HbA1c-related misdiagnosis or inappropriate management in up to 30 million Americans. Older adults, non-Hispanic Black individuals, and others with high mismatches may benefit from complementing HbA1c with additional diagnostic and management strategies.

Factors Associated with Unplanned Pregnancy Among Cancer Survivors.

Background: Approximately half of all pregnancies in the United States are unintended. However, women who are diagnosed with cancer in their reproductive years may be a unique population. This study examines the prevalence of and identifies factors associated with unplanned pregnancy among cancer survivors. Materials and Methods: Female cancer survivors aged 22-45 years, diagnosed between ages 20-35 years and at least 2 years postdiagnosis, and women with no history of cancer were interviewed about their reproductive histories, including pregnancy intention. Using a random matching process, comparison women were assigned an artificial age at cancer diagnosis equal to that of her cancer survivor match. An adjusted Cox model was fit examining time to unintended pregnancy after cancer for each of 1,000 matches. Cox proportional hazards models were also fit to assess associations between participant characteristics and unplanned pregnancy after cancer among survivors. Results: Cancer survivors (n = 1,282) and comparison women (n = 1,073) reported a similar likelihood of having an unplanned pregnancy in models adjusted for race, income, history of sexually-transmitted infection, and history of unplanned pregnancy before diagnosis (adjusted hazard ratio [aHR] 1.06, 95% simulation interval 0.85-1.36). After adjusting for confounders, unplanned pregnancy among survivors was associated with age <30 years at diagnosis (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.32-2.44), black race (HR: 1.55, 95% CI: 1.13-2.12; referent: white), receiving fertility counseling (aHR: 1.41, 95% CI: 1.04-1.92), and having at least one child before diagnosis (aHR: 1.44, 95% CI: 1.05-1.97). Conclusion: Cancer survivors and comparison women had similar likelihood of unplanned pregnancy. Rates of unplanned pregnancy after cancer were not higher for cancer survivors compared with comparison women, but 46.4% of survivors with a postcancer pregnancy reported an unplanned pregnancy. Cancer patients may benefit from patient-centered guidelines and counseling before cancer treatment that covers both risks of infertility and risks of unplanned pregnancy.

Influence of Paternal Race on Characteristics and Outcomes of Assisted Reproductive Technologies.

OBJECTIVE: To investigate the association between paternal race and reproductive outcomes following in vitro fertilization (IVF). MATERIALS AND METHODS: We compared demographic and clinical characteristics, IVF cycle characteristics, and reproductive outcomes (pregnancy, miscarriage, and live birth), stratified by male and female partner race, for all IVF cycles performed at our institution between 2014 and 2019. Wilcoxon Rank Sum test and Pearson's Chi Square test were used to compare continuous and categorical data, respectively. A Poisson regression model was used to determine the association between race and clinical outcomes. Significance was set as P <.05. RESULTS: We examined 1878 IVF cycles involving 1069 couples. The study population was diverse; 50.1% of male partners were white, 28.5% black, 15.1% Asian, and 2.3% Hispanic. The majority of couples (86.5%) shared a common self-reported race category. Black males were older than white males (39.6 vs 37.0 years), with higher BMI (30.4 vs 28.0) and higher frequency of male factor infertility (45.9% vs 33.5%). Female partners of black males were older than those of white males (35.6 vs 33.8 years), with higher BMI (29.6 vs 25.2), and higher frequency of female factor infertility (91.8% vs 83.9%). Although we noted race-related variability in IVF cycle characteristics, no significant differences in the outcomes of pregnancy, biochemical pregnancy, clinical intrauterine pregnancy, or ectopic pregnancy were observed between races. CONCLUSION: Although paternal race was associated with IVF cycle characteristics, after controlling for potential confounders, paternal race did not independently contribute to outcomes in this institutional dataset.

Urinary and salivary endocrine measurements to complement Tanner staging in studies of pubertal development.

BACKGROUND: Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development. OBJECTIVE: Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage. METHODS: Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007-2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis. RESULTS: Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3. CONCLUSIONS: Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset.

Influence of paternal age on assisted reproductive technology cycles and perinatal outcomes.

OBJECTIVE: To characterize paternal age among assisted reproductive technology (ART) cycles performed in the United States and to evaluate the influence of paternal age on ART cycles and perinatal outcomes. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): All reported fresh, nondonor, noncancelled in vitro fertilization (IVF) cycles performed in 2017. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The primary outcomes were intrauterine pregnancy, live birth (≥20 weeks), and miscarriage (<20 weeks) per cycle start and per embryo transfer. The secondary outcomes were full-term live birth (≥37 weeks) among singleton and twin gestations. Modified Poisson regression was performed to estimate associations between paternal age and cycle and perinatal outcomes, overall and stratified by maternal age. RESULT(S): Among 77,209 fresh nondonor, noncancelled IVF cycles, the average paternal age was 37.8 ± 6.3 years and the average maternal age was 35.5 ± 4.6 years. Compared with paternal age ≤45 years, paternal age ≥46 years was associated with a lower likelihood of pregnancy per cycle (adjusted risk ratio [aRR] 0.81; 95% confidence interval [CI] 0.76-0.87) and per transfer (aRR 0.85; 95% CI 0.81-0.90), as well as a lower likelihood of live birth per cycle (aRR 0.76; 95% CI 0.72-0.84) and per transfer (aRR 0.82; 95% CI 0.77-0.88) after controlling for maternal age and other confounders. When restricted to women aged <35 years, there were no significant differences in the rates of live birth or miscarriage among couples in which the men were aged ≤45 years compared with those aged ≥46 years. CONCLUSION(S): Compared with paternal age ≤45 years, paternal age ≥46 years is associated with a lower likelihood of pregnancy and live birth among couples undergoing IVF. The negative effect of paternal age is most notable among women aged ≥35 years, likely because maternal age is a stronger predictor of ART outcome.

Comparison of diameter-based and image-based measures of surface area from gross placental pathology for use in epidemiologic studies.

Placental surface area is often estimated using diameter measurements. However, as many placentas are not elliptical, we were interested in the validity of these estimates. We compared placental surface area from images for 491 singletons from the Stillbirth Collaborative Research Network (SCRN) Study (416 live births, 75 stillbirths) to estimates obtained using diameter measurements. Placental images and diameters were obtained from pathologic assessments conducted for the SCRN Study and images were analyzed using ImageJ software. On average, diameter-based measures underestimated surface area by -5.58% (95% confidence interval: -30.23, 19.07); results were consistent for normal and abnormal shapes. The association between surface area and birthweight was similar for both measures. Thus, diameter-based surface area can be used to estimate placental surface area.