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.

Implementation science: Scaling a training intervention to include IUDs and implants in contraceptive services in primary care.

Building capacity for contraceptive services in primary care settings, including for intrauterine devices (IUDs) and implants, can help to broaden contraceptive access across the US. Following a randomized trial in family planning clinics, we brought a provider training intervention to other clinical settings including primary care in all regions. This implementation science study evaluates a national scale-up of a contraceptive training intervention to varied practice settings from 2013 to 2019 among 3216 clinic staff serving an estimated 1.6 million annual contraceptive patients. We measured providers' knowledge and clinical practice changes regarding IUDs and implants using survey data. We estimated the overall intervention effect, and its relative effectiveness in primary care settings, with generalized estimating equations for clustered data. Patient-centered counseling improved, along with comfort with method provision and removal. Provider knowledge increased (p < 0.001), as did evidence-based counseling for IUDs (aOR 3.3 95% CI 2.8-3.9) and implants (aOR 3.5, 95% CI 3.0-4.1), and clinician competency in copper and levonorgestrel IUDs (aORs 1.8-2.6 95% CIs 1.5-3.2) and implants (aOR 2.4 95% CI 2.0-2.9). While proficiency was lower initially in primary care, gains were significant and at times greater than in Planned Parenthood health clinics. This intervention was effectively scaled, including in primary care settings with limited prior experience with these methods. Recent changes to Title X family planning funding rules exclude several large family planning providers, shifting greater responsibility to primary care and other settings. Scaling effective contraceptive interventions is one way to ensure capacity to offer patients full contraceptive services.