User login
SALT LAKE CITY – Both male and female recipients of childhood hematopoietic stem cell transplantation (HSCT) were very likely to have severely decreased fertility potential, even in the setting of preserved puberty, according to a recent study of adolescent and young adult HSCT recipients.
A reduced intensity conditioning regimen did not protect this cohort from decreased fertility, a finding that surprised the study’s lead author.
“We had hypothesized that, as compared to myeloablative conditioning, reduced intensity conditioning in children who received HSCT would lower the risk of infertility and lessen gonadal failure,” said Helen Oquendo del Toro, MD. In fact, Dr. Oquendo del Toro and her collaborators found that more than 90% of semen samples available for analysis had results that indicated infertility or severely impaired fertility, regardless of the type of pretransplant conditioning the patient had received.
The study highlights the need for fertility preservation when possible before HSCT, and makes clear that “normal puberty does not equate to normal fertility,” said Dr. Oquendo del Toro, of Cincinnati Children’s Hospital Medical Center.
Dr. Oquendo del Toro presented results of an observational cohort study of late effects of HSCT that included individuals aged 1-40 years old who received a single HSCT at, or after, 1 year of age.
Twenty-one males in the study had semen available for analysis. Of the 10 males who received myeloablative conditioning (MAC), 8 had azoospermia, and 2 more had oligoteratospermia (low sperm count with abnormal morphology). For the 11 males who received reduced intensity conditioning (RIC), eight had azoospermia, two had semen samples that showed oligoteratospermia, and one had a normal semen analysis.
The median age at transplant for these males was 14.5 years, and patients were a median of 19 years old at follow-up, Dr. Oquendo del Toro said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
For females in the study, low levels of anti-Müllerian hormone (AMH) – generally considered the best surrogate lab value for ovarian reserve – were nearly as common. Of 14 females receiving MAC, 13 (93%) had low AMH, as did 6 of 8 (75%) female patients who received RIC.
Individuals with more than one HSCT were excluded, as were those with Fanconi anemia, which itself carries a risk of gonadal failure. The study’s two aims were to investigate gonadal function as well as fertility potential after receipt of either RIC or MAC for HSCT.
Patients were seen by an endocrinologist who assessed testicular volume and assigned a Tanner stage. At age 11 and older, patients’ gonadal function was assessed on an annual basis by obtaining levels of luteinizing hormone and follicle stimulating hormone for all patients; female estradiol levels were tracked, as were male testosterone levels.
Assessment of fertility potential required additional laboratory testing: For females, the investigators obtained AMH levels, while for males, semen analysis was coupled with serum levels of inhibin B, an indicator of Sertoli cell function.
A total of 72 males were more than 1 year post-HSCT in the cohort, and of these, 41 were at least 11 years old and had achieved pubertal status according to laboratory evaluation. In all, 22 of the male patients received RIC, and 19 received MAC.
Males receiving MAC were a median 20 years old at their follow-up evaluation, and a median 6 years post-HSCT, while the RIC group were a median of 18.5 years old and 5.5 years out from their transplant.
Of the 50 females who were more than 1 year post-HSCT, 25 were pubertal and 11 years old or older. Nine of the female patients received RIC, and 16 received MAC.
Females who received MAC were a median 12.1 years old and 4.1 years post-HSCT at their follow-up evaluation. Females receiving RIC were a median 16 years old, and 6.5 years post-HSCT at the time of evaluation.
Patients received their transplants for a variety of malignant and nonmalignant conditions.
“We saw relatively normal gonadotropins after both reduced intensity and myeloablative conditioning in males,” Dr. Oquendo del Toro said. Of the MAC group, 4 of 15 (27%) had elevated follicle stimulating hormone levels, as did 2 of 17 (12%) of the RIC group. Elevated luteinizing hormone levels were seen in 2 of 15 (13%) of the MAC group and 1 of 17 (6%) of the RIC group. Four patients in each group had abnormally low testosterone levels.
However, when the investigators looked at inhibin B levels in males, they found abnormally low levels in 9 of 15 (60%) of those who received MAC, and in 6 of 15 (40%) of those who received RIC. These results meshed with the severely abnormal semen analyses investigators found from those participants for whom a sample was available, Dr. Oquendo del Toro said.
For females, estradiol levels were significantly lower for those who had received MAC, with 7 of 11 (64%) of that group having abnormally low estradiol levels. The levels approached 0 pg/mL for many, said Dr. Oquendo del Toro. None of the eight patients who had received RIC had abnormally low estradiol levels (P = .0008).
“Male puberty is relatively well preserved after both myeloablative and reduced intensity conditioning, but there is a greater than 90% risk of male infertility associated with both reduced intensity and myeloablative conditioning for HSCT,” Dr. Oquendo del Toro said.
For females, the study paints a different picture. “We saw decreased premature ovarian failure after reduced intensity conditioning … but the fertility potential as assessed by anti-Müllerian hormone was decreased” after both conditioning regimens, she said.
Dr. Oquendo del Toro reported having no conflicts of interest.
SOURCE: Oquendo del Toro H et al. The 2018 BMT Tandem Meetings, Abstract 88.
SALT LAKE CITY – Both male and female recipients of childhood hematopoietic stem cell transplantation (HSCT) were very likely to have severely decreased fertility potential, even in the setting of preserved puberty, according to a recent study of adolescent and young adult HSCT recipients.
A reduced intensity conditioning regimen did not protect this cohort from decreased fertility, a finding that surprised the study’s lead author.
“We had hypothesized that, as compared to myeloablative conditioning, reduced intensity conditioning in children who received HSCT would lower the risk of infertility and lessen gonadal failure,” said Helen Oquendo del Toro, MD. In fact, Dr. Oquendo del Toro and her collaborators found that more than 90% of semen samples available for analysis had results that indicated infertility or severely impaired fertility, regardless of the type of pretransplant conditioning the patient had received.
The study highlights the need for fertility preservation when possible before HSCT, and makes clear that “normal puberty does not equate to normal fertility,” said Dr. Oquendo del Toro, of Cincinnati Children’s Hospital Medical Center.
Dr. Oquendo del Toro presented results of an observational cohort study of late effects of HSCT that included individuals aged 1-40 years old who received a single HSCT at, or after, 1 year of age.
Twenty-one males in the study had semen available for analysis. Of the 10 males who received myeloablative conditioning (MAC), 8 had azoospermia, and 2 more had oligoteratospermia (low sperm count with abnormal morphology). For the 11 males who received reduced intensity conditioning (RIC), eight had azoospermia, two had semen samples that showed oligoteratospermia, and one had a normal semen analysis.
The median age at transplant for these males was 14.5 years, and patients were a median of 19 years old at follow-up, Dr. Oquendo del Toro said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
For females in the study, low levels of anti-Müllerian hormone (AMH) – generally considered the best surrogate lab value for ovarian reserve – were nearly as common. Of 14 females receiving MAC, 13 (93%) had low AMH, as did 6 of 8 (75%) female patients who received RIC.
Individuals with more than one HSCT were excluded, as were those with Fanconi anemia, which itself carries a risk of gonadal failure. The study’s two aims were to investigate gonadal function as well as fertility potential after receipt of either RIC or MAC for HSCT.
Patients were seen by an endocrinologist who assessed testicular volume and assigned a Tanner stage. At age 11 and older, patients’ gonadal function was assessed on an annual basis by obtaining levels of luteinizing hormone and follicle stimulating hormone for all patients; female estradiol levels were tracked, as were male testosterone levels.
Assessment of fertility potential required additional laboratory testing: For females, the investigators obtained AMH levels, while for males, semen analysis was coupled with serum levels of inhibin B, an indicator of Sertoli cell function.
A total of 72 males were more than 1 year post-HSCT in the cohort, and of these, 41 were at least 11 years old and had achieved pubertal status according to laboratory evaluation. In all, 22 of the male patients received RIC, and 19 received MAC.
Males receiving MAC were a median 20 years old at their follow-up evaluation, and a median 6 years post-HSCT, while the RIC group were a median of 18.5 years old and 5.5 years out from their transplant.
Of the 50 females who were more than 1 year post-HSCT, 25 were pubertal and 11 years old or older. Nine of the female patients received RIC, and 16 received MAC.
Females who received MAC were a median 12.1 years old and 4.1 years post-HSCT at their follow-up evaluation. Females receiving RIC were a median 16 years old, and 6.5 years post-HSCT at the time of evaluation.
Patients received their transplants for a variety of malignant and nonmalignant conditions.
“We saw relatively normal gonadotropins after both reduced intensity and myeloablative conditioning in males,” Dr. Oquendo del Toro said. Of the MAC group, 4 of 15 (27%) had elevated follicle stimulating hormone levels, as did 2 of 17 (12%) of the RIC group. Elevated luteinizing hormone levels were seen in 2 of 15 (13%) of the MAC group and 1 of 17 (6%) of the RIC group. Four patients in each group had abnormally low testosterone levels.
However, when the investigators looked at inhibin B levels in males, they found abnormally low levels in 9 of 15 (60%) of those who received MAC, and in 6 of 15 (40%) of those who received RIC. These results meshed with the severely abnormal semen analyses investigators found from those participants for whom a sample was available, Dr. Oquendo del Toro said.
For females, estradiol levels were significantly lower for those who had received MAC, with 7 of 11 (64%) of that group having abnormally low estradiol levels. The levels approached 0 pg/mL for many, said Dr. Oquendo del Toro. None of the eight patients who had received RIC had abnormally low estradiol levels (P = .0008).
“Male puberty is relatively well preserved after both myeloablative and reduced intensity conditioning, but there is a greater than 90% risk of male infertility associated with both reduced intensity and myeloablative conditioning for HSCT,” Dr. Oquendo del Toro said.
For females, the study paints a different picture. “We saw decreased premature ovarian failure after reduced intensity conditioning … but the fertility potential as assessed by anti-Müllerian hormone was decreased” after both conditioning regimens, she said.
Dr. Oquendo del Toro reported having no conflicts of interest.
SOURCE: Oquendo del Toro H et al. The 2018 BMT Tandem Meetings, Abstract 88.
SALT LAKE CITY – Both male and female recipients of childhood hematopoietic stem cell transplantation (HSCT) were very likely to have severely decreased fertility potential, even in the setting of preserved puberty, according to a recent study of adolescent and young adult HSCT recipients.
A reduced intensity conditioning regimen did not protect this cohort from decreased fertility, a finding that surprised the study’s lead author.
“We had hypothesized that, as compared to myeloablative conditioning, reduced intensity conditioning in children who received HSCT would lower the risk of infertility and lessen gonadal failure,” said Helen Oquendo del Toro, MD. In fact, Dr. Oquendo del Toro and her collaborators found that more than 90% of semen samples available for analysis had results that indicated infertility or severely impaired fertility, regardless of the type of pretransplant conditioning the patient had received.
The study highlights the need for fertility preservation when possible before HSCT, and makes clear that “normal puberty does not equate to normal fertility,” said Dr. Oquendo del Toro, of Cincinnati Children’s Hospital Medical Center.
Dr. Oquendo del Toro presented results of an observational cohort study of late effects of HSCT that included individuals aged 1-40 years old who received a single HSCT at, or after, 1 year of age.
Twenty-one males in the study had semen available for analysis. Of the 10 males who received myeloablative conditioning (MAC), 8 had azoospermia, and 2 more had oligoteratospermia (low sperm count with abnormal morphology). For the 11 males who received reduced intensity conditioning (RIC), eight had azoospermia, two had semen samples that showed oligoteratospermia, and one had a normal semen analysis.
The median age at transplant for these males was 14.5 years, and patients were a median of 19 years old at follow-up, Dr. Oquendo del Toro said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.
For females in the study, low levels of anti-Müllerian hormone (AMH) – generally considered the best surrogate lab value for ovarian reserve – were nearly as common. Of 14 females receiving MAC, 13 (93%) had low AMH, as did 6 of 8 (75%) female patients who received RIC.
Individuals with more than one HSCT were excluded, as were those with Fanconi anemia, which itself carries a risk of gonadal failure. The study’s two aims were to investigate gonadal function as well as fertility potential after receipt of either RIC or MAC for HSCT.
Patients were seen by an endocrinologist who assessed testicular volume and assigned a Tanner stage. At age 11 and older, patients’ gonadal function was assessed on an annual basis by obtaining levels of luteinizing hormone and follicle stimulating hormone for all patients; female estradiol levels were tracked, as were male testosterone levels.
Assessment of fertility potential required additional laboratory testing: For females, the investigators obtained AMH levels, while for males, semen analysis was coupled with serum levels of inhibin B, an indicator of Sertoli cell function.
A total of 72 males were more than 1 year post-HSCT in the cohort, and of these, 41 were at least 11 years old and had achieved pubertal status according to laboratory evaluation. In all, 22 of the male patients received RIC, and 19 received MAC.
Males receiving MAC were a median 20 years old at their follow-up evaluation, and a median 6 years post-HSCT, while the RIC group were a median of 18.5 years old and 5.5 years out from their transplant.
Of the 50 females who were more than 1 year post-HSCT, 25 were pubertal and 11 years old or older. Nine of the female patients received RIC, and 16 received MAC.
Females who received MAC were a median 12.1 years old and 4.1 years post-HSCT at their follow-up evaluation. Females receiving RIC were a median 16 years old, and 6.5 years post-HSCT at the time of evaluation.
Patients received their transplants for a variety of malignant and nonmalignant conditions.
“We saw relatively normal gonadotropins after both reduced intensity and myeloablative conditioning in males,” Dr. Oquendo del Toro said. Of the MAC group, 4 of 15 (27%) had elevated follicle stimulating hormone levels, as did 2 of 17 (12%) of the RIC group. Elevated luteinizing hormone levels were seen in 2 of 15 (13%) of the MAC group and 1 of 17 (6%) of the RIC group. Four patients in each group had abnormally low testosterone levels.
However, when the investigators looked at inhibin B levels in males, they found abnormally low levels in 9 of 15 (60%) of those who received MAC, and in 6 of 15 (40%) of those who received RIC. These results meshed with the severely abnormal semen analyses investigators found from those participants for whom a sample was available, Dr. Oquendo del Toro said.
For females, estradiol levels were significantly lower for those who had received MAC, with 7 of 11 (64%) of that group having abnormally low estradiol levels. The levels approached 0 pg/mL for many, said Dr. Oquendo del Toro. None of the eight patients who had received RIC had abnormally low estradiol levels (P = .0008).
“Male puberty is relatively well preserved after both myeloablative and reduced intensity conditioning, but there is a greater than 90% risk of male infertility associated with both reduced intensity and myeloablative conditioning for HSCT,” Dr. Oquendo del Toro said.
For females, the study paints a different picture. “We saw decreased premature ovarian failure after reduced intensity conditioning … but the fertility potential as assessed by anti-Müllerian hormone was decreased” after both conditioning regimens, she said.
Dr. Oquendo del Toro reported having no conflicts of interest.
SOURCE: Oquendo del Toro H et al. The 2018 BMT Tandem Meetings, Abstract 88.
REPORTING FROM THE 2018 BMT TANDEM MEETINGS
Key clinical point:
Major finding: Of 21 males receiving reduced intensity conditioning or myeloablative conditioning, all but one had azoospermia or oligoteratospermia.
Study details: Observational cohort study of 41 males and 25 females receiving pediatric HSCT.
Disclosures: Dr. Oquendo del Toro reported having no conflicts of interest.
Source: Oquendo del Toro H et al. The 2018 BMT Tandem Meetings, Abstract 88.