SUN-266 Anti-Mullerian Hormone as a Marker of Ovarian Reserve in Female Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Abstract

Background/Methods: Gonadal dysfunction leading to infertility is a common complication after hematopoietic stem cell transplant (HSCT). Previous work by our group has shown that there is a significantly higher risk of delayed puberty and premature ovarian insufficiency among girls who receive high intensity, myeloablative conditioning (MAC) regimens compared to reduced intensity conditioning (RIC) regimens. Anti-Müllerian Hormone (AMH) is not regulated by gonadotropins and has minimal inter-cycle variations; therefore, it can be used as a marker of follicular ovarian reserve and aid in fertility counseling. We sought to assess ovarian reserve utilizing AMH levels in a retrospective study of female pediatric patients undergoing HSCT from 2013-2017 who received either MAC or RIC regimens. Results: In total, 100 female patients with a median age of 7 years had AMH levels pre-HSCT, of whom 33 (33%) also had post-HSCT levels. A wide variety of diagnoses were included: 32% had malignancy; 19% had immunodeficiency; 17% had Fanconi anemia (FA), 17% had hemoglobinopathy; 12% had non-FA marrow failure, and 3% had a metabolic disorder. Among those with pre-HSCT AMH levels, 71 (71%) had normal AMH for age, and 29 (29%) had low AMH for age. Of the 33 patients who also had post-HSCT AMH, 24 (72%) had low levels following transplantation. Twenty-five patients had both a normal pre-HSCT AMH and subsequent post-HSCT levels performed, 13 of whom (52%) received a MAC regimen and 12 of whom (48%) received RIC regimen. All (13/13) of the patients who received a MAC regimen had low AMH post-HSCT, while only 25% (3/12) of the patients who received a RIC regimen had low AMH post-HSCT (p=0.0002). Eight patients had both a low pre-HSCT AMH and subsequent post-HSCT AMH levels performed, 5 of whom received a MAC regimen and 3 of whom received a RIC regimen. All subject with low pre-HSCT AMH levels additionally had low post-HSCT AMH regardless of conditioning regimen used. Conclusions: AMH levels can be a useful marker for detection of low ovarian reserve and fertility counseling, especially if trends are followed before and after exposure to alkylating agents used for HSCT preparation. Our data show a significantly higher risk of low, downtrending AMH after exposure to high intensity MAC regimens compared to RIC regimens during childhood HSCT, which likely indicates a greater potential for infertility in patients receiving MAC regimens. These data correlate with a previous analysis demonstrating a significantly higher incidence of premature ovarian insufficiency and delayed puberty among girls receiving MAC regimens vs RIC regimens. Long-term follow up of this cohort will provide more information to understand the effects of HSCT on ovarian function and the utility of AMH as a predictor of future fertility potential.