Outcomes after assisted reproductive technology in women with cancer: A systematic review and meta-Analysis

STUDY QUESTION: What are the associations between a history of cancer and outcomes after ART? SUMMARY ANSWER: Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART. WHAT IS KNOWN ALREADY: Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes. STUDY DESIGN, SIZE, DURATION: We conducted a systematic review with meta-Analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-Analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-Adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-And-fill method to assess funnel plot asymmetry. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage. LIMITATIONS, REASONS FOR CAUTION: Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests. REGISTRATION NUMBER: N/A

Disparities in the use of assisted reproductive technologies after breast cancer: a population-based study

Purpose: Equitable access to oncofertility services is a key component of cancer survivorship care, but factors affecting access and use remain understudied. Methods: To describe disparities in assisted reproductive technology (ART) use among women with breast cancer in California, we conducted a population-based cohort study using linked oncology, ART, and demographic data. We identified women age 18–45 years diagnosed with invasive breast cancer between 2000 and 2015. The primary outcome was ART use—including oocyte/embryo cryopreservation or embryo transfer—after cancer diagnosis. We used log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to identify factors associated with ART use. Results: Among 36,468 women with invasive breast cancer, 206 (0.56%) used ART. Women significantly less likely to use ART were age 36–45 years at diagnosis (vs. 18–35 years: PR = 0.17, 95% CI 0.13–0.22); non-Hispanic Black or Hispanic (vs. non-Hispanic White: PR = 0.31, 95% CI 0.21–0.46); had at least one child (vs. no children: adjusted PR [aPR] = 0.39, 95% CI 0.25–0.60); or lived in non-urban areas (vs. urban: aPR = 0.28, 95% CI 0.10–0.75), whereas women more likely to use ART lived in high-SES areas (vs. low-/middle-SES areas: aPR = 2.93, 95% CI 2.04–4.20) or had private insurance (vs. public/other insurance: aPR = 2.95, 95% CI 1.59–5.49). Conclusion: Women with breast cancer who are socially or economically disadvantaged, or who already had a child, are substantially less likely to use ART after diagnosis. The implementation of policies or programs targeting more equitable access to fertility services for women with cancer is warranted

Disparities in Fertility-Sparing Treatment and Use of Assisted Reproductive Technology After a Diagnosis of Cervical, Ovarian, or Endometrial Cancer

Objective: To assess the presence of sociodemographic and clinical disparities in fertility-sparing treatment and assisted reproductive technology (ART) use among patients with a history of cervical, endometrial, or ovarian cancer. Methods: We conducted a population-based cohort study of patients aged 18-45 years who were diagnosed with cervical cancer (stage IA, IB), endometrial cancer (grade 1, stage IA, IB), or ovarian cancer (stage IA, IC) between January 1, 2000, and December 31, 2015, using linked data from the CCR (California Cancer Registry), the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. The primary outcome was receipt of fertility-sparing treatment, defined as surgical or medical treatment to preserve the uterus and at least one ovary. The secondary outcome was fertility preservation, defined as ART use after cancer diagnosis. Multivariable logistic regression analysis was used to estimate odds ratios and 95% CIs for the association between fertility-sparing treatment and exposures of interest: age at diagnosis, race and ethnicity, health insurance, socioeconomic status, rurality, and parity. Results: We identified 7,736 patients who were diagnosed with cervical, endometrial, or ovarian cancer with eligible histology. There were 850 (18.8%) fertility-sparing procedures among 4,521 cases of cervical cancer, 108 (7.2%) among 1,504 cases of endometrial cancer, and 741 (43.3%) among 1,711 cases of ovarian cancer. Analyses demonstrated nonuniform patterns of sociodemographic disparities by cancer type for fertility-sparing treatment, and ART. Fertility-sparing treatment was more likely among young patients, overall, and of those in racial and ethnic minority groups among survivors of cervical and ovarian cancer. Use of ART was low (n=52) and was associated with a non-Hispanic White race and ethnicity designation, being of younger age (18-35 years), and having private insurance. Conclusion: This study demonstrates that clinical and sociodemographic disparities exist in the receipt of fertility-sparing treatment and ART use among patients with a history of cervical, endometrial, or ovarian cancer

Obstetric and Neonatal Outcomes 1 or More Years After a Diagnosis of Breast Cancer

OBJECTIVE:To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis.METHODS:We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December 31, 2012, and conceived 12 or more months after breast cancer diagnosis. Individuals in the control group were covariate-matched women without a history of breast cancer who delivered during 2000-2012. The primary outcome was preterm birth at less than 37 weeks of gestation. Secondary outcomes were preterm birth at less than 32 weeks of gestation, small for gestational age (SGA), cesarean delivery, severe maternal morbidity, and neonatal morbidity. Subgroup analyses were used to assess the effect of time from initial treatment to fertilization and receipt of additional adjuvant therapy before pregnancy on outcomes of interest.RESULTS:Of 30,021 women aged 18-45 years diagnosed with stage I-III breast cancer during 2000-2012, 553 met the study inclusion criteria. Those with a history of breast cancer and matched women in the control group had similar odds of preterm birth at less than 37 weeks of gestation (odds ratio [OR], 1.29; 95% CI 0.95-1.74), preterm birth at less than 32 weeks of gestation (OR 0.77; 95% CI 0.34-1.79), delivering an SGA neonate (less than the 5th percentile: OR 0.60; 95% CI 0.35-1.03; less than the 10th percentile: OR 0.94; 95% CI 0.68-1.30), and experiencing severe maternal morbidity (OR 1.61; 95% CI 0.74-3.50). Patients with a history of breast cancer had higher odds of undergoing cesarean delivery (OR 1.25; 95% CI 1.03-1.53); however, their offspring did not have increased odds of neonatal morbidity compared with women in the control group (OR 1.15; 95% CI 0.81-1.62).CONCLUSION:Breast cancer 1 or more years before fertilization was not strongly associated with obstetric and neonatal complications