Introduction Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health needs of emerging adult female survivors of childhood cancer and to identify decisional and contextual factors that influence pursuit of FSA using an explanatory sequential quantitative to qualitative mixed methods design. Methods and analysis This study will enroll 325 female survivors (aged 18 to 29 years and >1-year post treatment; diagnosed with cancer < age 21 years) from four cancer centers in the United States. Sociodemographic and developmental factors, reproductive knowledge and values, decisional needs, and receipt of an FSA will be assessed through a web-based survey. Informed by survey findings, a subset of participants will be recruited for qualitative interviews to explore decisional factors associated with uptake of an FSA. Clinical data will be abstracted from the medical records. Multivariable logistic regression models will be developed to identify factors associated with FSA and qualitative descriptive analysis will be used to develop themes from the interviews. Quantitative and qualitative findings will be merged using a joint display to develop integrated study conclusions and direct future interventional research.
Objective: Women with SLE may experience ovarian insufficiency or dysfunction due to treatment or disease effects. Anti-Müllerian hormone (AMH), a marker of ovarian reserve, has been examined in small populations of women with SLE with conflicting results. To date, these studies have included very few African-American women, the racial/ethnic group at greatest risk of SLE. Methods: We enrolled African-American women aged 22-40 years diagnosed with SLE after age 17 from the Atlanta Metropolitan area. Women without SLE from the same area were recruited from a marketing list for comparison. AMH was measured in serum using the Ansh Labs assay (Webster, Texas, USA). We considered AMH levels <1.0 ng/mL and AMH <25th percentile of comparison women as separate dichotomous outcomes. Log-binomial regression models estimating prevalence ratios were adjusted for age, body mass index and hormonal contraception use in the previous year. Results: Our sample included 83 comparison women without SLE, 68 women with SLE and no history of cyclophosphamide (SLE/CYC-) and 11 women with SLE and a history of cyclophosphamide treatment (SLE/CYC+). SLE/CYC+ women had a greater prevalence of AMH <1.0 ng/mL compared with women without SLE (prevalence ratio (PR): 2.90, 95% CI: 1.29 to 6.51). SLE/CYC- women were also slightly more likely to have AMH <1.0 ng/mL (PR: 1.62, 95% CI: 0.93 to 2.82) than comparison women. Results were similar when considering AMH <25th percentile by age of comparison women. Conclusions: Treatment with CYC is associated with low AMH in African-American women with SLE. SLE itself may also be associated with reduced AMH, but to a lesser extent.
Objective: To identify modifying genes that explains the risk of fragile X-associated primary ovarian insufficiency (FXPOI). Design: Gene-based, case/control association study, followed by a functional screen of highly ranked genes using a Drosophila model. Setting: Participants were recruited from academic and clinical settings. Patient(s): Women with a premutation (PM) who experienced FXPOI at the age of 35 years or younger (n = 63) and women with a PM who experienced menopause at the age of 50 years or older (n = 51) provided clinical information and a deoxyribonucleic acid sample for whole genome sequencing. The functional screen was on the basis of Drosophila TRiP lines. Intervention(s): Clinical information and a DNA sample were collected for whole genome sequencing. Main Outcome Measures: A polygenic risk score derived from common variants associated with natural age at menopause was calculated and associated with the risk of FXPOI. Genes associated with the risk of FXPOI were identified on the basis of the P-value from gene-based association test and an altered level of fecundity when knocked down in the Drosophila PM model. Results: The polygenic risk score on the basis of common variants associated with natural age at menopause explained approximately 8% of the variance in the risk of FXPOI. Further, SUMO1 and KRR1 were identified as possible modifying genes associated with the risk of FXPOI on the basis of an untargeted gene analysis of rare variants. Conclusions: In addition to the large genetic effect of a PM on ovarian function, the additive effects of common variants associated with natural age at menopause and the effect of rare modifying variants appear to play a role in FXPOI risk.
Objective: Some treatments for systemic lupus erythematosus (SLE) can cause infertility, but the effect of SLE itself on fertility, particularly in African American women, is less clear. We undertook this study to examine infertility experiences in African American women with SLE compared to healthy women. Methods: We enrolled women ages 22–40 years living in the Atlanta metropolitan area who were diagnosed with SLE after age 17 years. Women who had ever been treated with cyclophosphamide or who had a hysterectomy were excluded. African American women ages 22–40 years who were from the same area and recruited from a marketing list were used for comparison. Women were interviewed about their reproductive histories and goals. Periods of infertility were identified as times when women had regular, unprotected sex for ≥12 months without conceiving after 20 years of age. We separately considered any period of infertility and periods of infertility when attempting pregnancy. We used Cox proportional hazards regression to examine the association between SLE and time to infertility. Models were adjusted for age, nulliparity, and smoking. An age-matched analysis was also conducted to examine periods of infertility occurring after SLE diagnosis. Results: Our sample included 75 women with SLE and 154 women without SLE. SLE was associated with any infertility (adjusted hazard ratio [HRadj] 2.08 [95% confidence interval (95% CI) 1.38–3.15]), but less so with infertility when attempting pregnancy (HRadj 1.30 [95% CI 0.62–2.71]). The matched analysis generated similar point estimates. Conclusion: Women with SLE may be more likely to experience episodes of infertility, but this may not translate to an inability to meet reproductive goals.
Objective: To investigate the effects of oocyte donor and recipient body mass index (BMI) on outcomes of vitrified donor oocyte assisted reproductive technology (ART). Design: Retrospective cohort study. Setting: Private fertility center. Patient(s): A total of 338 oocyte donors and 932 recipients who underwent 1,651 embryo transfer cycles in 2008–2015. Intervention(s): Multivariable log binomial regression models with cluster-weighted generalized estimating equations were used to estimate the adjusted risk ratios. Main Outcome Measure(s): Live birth, defined as the delivery of at least one live-born infant, including all embryo transfer cycles. Secondary outcomes included birth weight and gestational length only among singleton live births. Results: The mean ± SD body mass indexes (BMIs) of donors and recipients were 22.6 ± 2.5 kg/m2 and 24.6 ± 4.8 kg/m2, respectively. There were no significant associations between donor BMI and probability of live birth. Recipients with BMI ≥35 kg/m2 had a significantly higher probability of live birth compared with normal-weight recipients. Among singleton live births, recipients with BMI <18.5 kg/m2 had a lower risk whereas women with BMI ≥35 kg/m2 had a higher risk of delivery in an earlier gestational week compared with normal weight women. Recipients with a BMI ≥35 kg/m2 also had a higher risk of having a low birth weight infant compared with normal-weight women. Conclusions: In the setting of vitrified donor oocyte ART, recipient BMI was positively associated with probability of live birth but negatively associated with gestational length and birth weight among singleton births.
It is unclear whether cancer and its treatments increase the risk of adverse pregnancy outcomes. Our aim was to examine whether cancer survivors have higher risks of poor outcomes in pregnancies conceived after diagnosis than women without cancer, and whether these risks differ by cancer type and race. Diagnoses from cancer registries were linked to pregnancy outcomes from birth certificates in three U.S. states. Analyses were limited to the first, live singleton birth conceived after diagnosis. Births to women without a previous cancer diagnosis in the registry were matched to cancer survivors on age at delivery, parity, race/ethnicity and education. Log-binomial regression was used to estimate risk ratios. Cervical cancer survivors had higher risks of preterm birth (Risk ratio = 2.8, 95% Confidence interval: 2.1, 3.7), as did survivors of invasive breast cancer (RR = 1.3, 95% CI: 1.1, 1.7) and leukemia (RR = 2.1, 95% CI: 1.3, 3.5). We observed a higher risk of small for gestational age (SGA) infants (<10% of weight for age based on a national distribution) in survivors of brain cancer (RR = 1.7, 95% CI: 1.1, 2.8) and extranodal non-Hodgkin lymphoma (RR = 2.3, 95% CI: 1.5, 3.6). We did not see an increased risk of infants born preterm, low birth weight, or SGA in pregnancies conceived after ductal carcinoma in situ, thyroid cancer, melanoma, or Hodgkin lymphoma. While our results are reassuring for survivors of many cancers, some will need closer monitoring during pregnancy.
Background: A growing literature suggests that minority races, particularly Black women, have a lower probability of live birth and higher risk of perinatal complications after autologous assisted reproductive technology. However, questions still remain as to whether these racial disparities have arisen because of associations between race and oocyte/embryo quality, the uterine environment, or a combination of the two. Oocyte donation assisted reproductive technology represents a unique approach to examine this question. Objective: This study aimed to evaluate the associations between the race of female oocyte donors and recipients and live birth rates following vitrified donor oocyte assisted reproductive technologies. Study Design: This was a retrospective study conducted at a single, private fertility clinic that included 327 oocyte donors and 899 recipients who underwent 1601 embryo transfer cycles (2008–2015). Self-reported race of the donor and recipient were abstracted from medical records. Live birth was defined as the delivery of at least 1 live-born neonate. We used multivariable cluster weighted generalized estimating equations with binomial distribution and log link function to estimate the adjusted risk ratios of live birth, adjusting for donor age and body mass index, recipient age and body mass index, tubal and uterine factor infertility, and year of oocyte retrieval. Results: The racial profile of our donors and recipients were similar: 73% white, 13% Black, 4% Hispanic, 8% Asian, and 2% other. Women who received oocytes from Hispanic donors had a significantly higher probability of live birth (adjusted risk ratio, 1.20; 95% confidence interval, 1.05–1.36) than women who received oocytes from white donors. Among Hispanic recipients, however, there was no significant difference in probability of live birth compared with white recipients (adjusted risk ratio, 1.07; 95% confidence interval, 0.90–1.26). Embryo transfer cycles using oocytes from Black donors (adjusted risk ratio, 0.86; 95% confidence interval, 0.72–1.03) and Black recipients (adjusted risk ratio, 0.84; 95% confidence interval, 0.71–0.99) had a lower probability of live birth than white donors and white recipients, respectively. There were no significant differences in the probability of live birth among Hispanic, Asian, and other race recipients compared with white recipients. Conclusion: Black female recipients had a lower probability of live birth following assisted reproductive technology, even when using vitrified oocytes from healthy donors. Female recipients who used vitrified oocytes from Hispanic donors had a higher probability of live birth regardless of their own race.
Background
The aim of this retrospective cohort study was to determine whether women who conceive soon after treatment have higher risks of adverse pregnancy outcomes.
Methods
Vital records data were linked to cancer registry diagnosis and treatment information in three U.S. states. The first pregnancy conceived after diagnosis between ages 20–45 years with any invasive cancer or ductal carcinoma in situ was eligible. Log-binomial models were used to compare risks in cancer survivors who conceived in each interval to the risks in matched comparison births to women without cancer.
Results
Women who conceived ≤1 year after starting chemotherapy for any cancer had higher risks of preterm birth than comparison women (RR for chemotherapy alone=1.9, 95% CI: 1.3, 2.7; RR for chemotherapy with radiation=2.4, 95% CI: 1.6, 3.6); women who conceived ≥1 year after starting chemotherapy without radiation or ≥2 years after chemotherapy with radiation did not. In analyses imputing treatment end date for breast cancer survivors, those who conceived ≥1 year after finishing chemotherapy with or without radiation had no higher risks than women without cancer. The risk of preterm birth in cervical cancer survivors largely persisted but was somewhat lower in pregnancies conceived after the first year (RR for pregnancies conceived ≤1 year after diagnosis=3.5, 95% CI: 2.2, 5.4; RR for pregnancies conceived >1 year=2.4, 95% CI: 1.6, 3.5).
Conclusions
In women who received chemotherapy, the higher risk of preterm birth was limited to those survivors with short intervals between treatment and conception.
OBJECTIVE: Systemic lupus erythematosus (SLE) disproportionately affects women and often develops during their reproductive years. Research suggests that some women who receive cyclophosphamide as treatment for SLE experience earlier decline in menstrual function, but reproductive health among women with SLE who have not taken this drug is less well understood. This study aims to better understand the relation between SLE and reproduction by assessing early secondary amenorrhoea and pregnancy in women treated with and without cyclophosphamide from a population-based cohort with large numbers of African-Americans.
METHODS: Female patients with SLE, ages 20-40 at time of diagnosis, who were 40 years or older at the time of the survey were included in this analysis (N=147). Participants in the Georgians Organized Against Lupus (GOAL) study were asked about their reproductive histories including early secondary amenorrhoea, defined as loss of menstruation before age 40.
RESULTS: Women who were cyclophosphamide naïve had an increased prevalence of early secondary amenorrhoea compared with population estimates, 13-17% compared with 1-5%. Factors associated with early secondary amenorrhoea in women not treated with cyclophosphamide were marital status and receipt of a kidney transplant. Treatment with cyclophosphamide doubled the prevalence after adjustment for patient characteristics. Over 88% of women reported being pregnant at least once, and about 83% of these had a child, but the majority of pregnancies occurred before diagnosis.
CONCLUSIONS: SLE diagnosed in early adulthood may affect women's reproductive health even if they are not treated with cyclophosphamide. Better understanding of other factors related to reproductive health in this population will improve clinicians' and patients' abilities to make treatment and family planning decisions.
Many patients with cystic fibrosis (CF) are living well into their adult years and contemplating parenthood. Previous studies have shown that there is an opportunity to improve understanding of inheritance and genetics among individuals with CF. This study explored whether a genetic counselling intervention would be associated with a change in knowledge and/or beliefs about genetics and family-building options. Adults (age ≥ 18 years) presenting to a CF clinic were approached for inclusion. Participants completed a pre-intervention survey to measure their knowledge of CF genetics, as well as perceptions and understanding of assisted reproductive technology treatments and other family-building options. Subjects then partook in a genetic counselling session. Subjects repeated the survey immediately after the session and 1–3 months later. Data analysis used one-way analysis of variance (ANOVA), repeated measures ANOVA and multiple linear regression. Thirty-five subjects [19 (54%) men and 16 (45%) women] with a mean (±standard deviation) age of 28 ± 5.64 years were enrolled in the study. Before the intervention, 61.69% ± 4.50 of knowledge-based questions were answered correctly. Immediately after the intervention, the mean score increased to 77.71% ± 3.23, but this decreased to 69.48% ± 4.02 for the third test (P < 0.05, repeated measures ANOVA). Six individuals changed their family-building preference following the genetic counselling session. A short genetic consultation was associated with a significant improvement in CF-specific genetic knowledge. However, knowledge was not retained fully for a longer time period following the consultation. Multiple discussions regarding fertility options are needed to reinforce the key concepts related to CF genetics and fertility.