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Ovarian function in pediatric brain cancer survivors after laparoscopic oophoropexy
Conclusion: Our results suggest that LIF gene mutations can lead to embryo implantation failure and that way to primary infertility and decreased pregnancy rates in assisted reproduction techniques. As long as LIF can be locally substituted in the transfer medium at the time of embryo transfer, our study contributes to progress in assisted reproduction techniques. Supported by: Grant Agency of the Czech Republic, Grant No. 301/02/ 1232, Charles University, Institutional Research Concept No. VZ 111400005(6035), Czech Academy of Sciences, Institutional Research Concept No. AV0Z5020903.
Wednesday, October 15, 2003 4:15 P.M. O-234 Causes of infertility and ovarian cancer risk. Louise A. Brinton, Emmet J. Lamb, Kamran S. Moghissi, Humberto Scoccia, Carolyn Westhoff, Michelle Althuis. National Cancer Institute, Bethesda, MD; Stanford Univ, Stanford, CA; Wayne State Univ, Detroit, MI; Univ of Illinois at Chicago, Chicago, IL; Columbia Univ, New York, NY. Objective: Evaluation of the risk of ovarian cancer associated with different underlying causes of infertility after adjustment for other risk factors. Design: A standardized algorithm was used to determine causes of infertility from medical records of 12,193 women evaluated between 1965-88 at five clinical sites. Causes were assigned according to the following prioritized scheme: 1) endometriosis, 2) ovulation disorders, 3) tubal disease and pelvic adhesions, 4) male factor or uterine/cervical disorders, and 5) unexplained causes/incomplete work-ups. Follow-up through 1999 via patient questionnaires and linkage against cancer and death registries identified 44 ovarian cancers diagnosed one or more years after first clinic visit. Materials and Methods: Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) compared ovarian cancer risk in the cohort of infertile women to that of U.S. women. Within the study population of infertile women, the different causes of infertility were evaluated by estimating relative risks (RR) of ovarian cancer for different causes of infertility after adjustment for other predictors of risk. Results: Infertile patients were found to be at a significantly high risk of ovarian cancer compared with women in the general population (SIR ⫽ 2.0, 95% CI 1.8-4.0), with the risk higher for patients with primary (SIR ⫽ 2.7) than secondary infertility (SIR ⫽ 1.5). Among infertile women, patients with endometriosis (22% of subjects) were at highest risk of developing ovarian cancer when compared to those with only male factor or uterine/ cervical disorders (14%), with a RR of 1.7 (95% CI 0.6-4.8). This risk was considerably higher than that observed among patients with anovulatory problems (22% of subjects) or tubal disease (16%), who had RRs of only 1.2-1.3. Ovarian cancer risks, however, were higher among patients with primary infertility if causes were attributed to either endometriosis (RR ⫽ 2.3) or tubal disease (RR ⫽ 2.2). In contrast, ovarian cancer risks were elevated among secondary infertility patients diagnosed with anovulatory problems (RR ⫽ 1.7). Subjects with unknown causes or incomplete workups (22%) were also found to be at elevated risk (RR ⫽ 1.8, 95 % CI 0.6-5.1), with no variation according to primary or secondary infertility. The risks associated with different causes of infertility were not changed after adjustment for other ovarian cancer risk factors, including gravidity or parity at follow-up, socioeconomic status, gynecologic operations, oral contraceptive use, and exposure to infertility medications. Conclusion: Determination of ovarian cancer risk should take into account the underlying causes of infertility. Further study of endometriosis in relation to ovarian cancer may provide insights into carcinogenic mechanisms. Supported by: NIH/NCI intramural funding provided through the U.S. government.
Wednesday, October 15, 2003 4:30 P.M. O-235 Ovarian function in pediatric brain cancer survivors after laparoscopic oophoropexy. Wendy Kuohung, Marc R. Laufer, Karen J. Marcus, Debbie
S90
Abstracts
M. Cheng, Lisa R. Diller. Brigham & Women’s Hosp, Boston, MA; Brigham & Women’s Hosp, Children’s Hosp, Boston, MA; Children’s Hosp, Boston, MA; Boston Univ Sch of Public Health, Boston, MA; Dana-Farber Cancer Institute, Boston, MA. Objective: Cancer of the nervous system is the most common solid tumor in children and often is treated with craniospinal radiation after surgical resection. Radiation-induced ovarian failure has been reported to occur in 60% of female cancer survivors receiving spinal radiation. We aimed to determine whether laparoscopic unilateral oophoropexy prior to radiotherapy effectively spares ovarian function from radiation damage. Design: Retrospective analysis of girls aged 16 and younger receiving craniospinal radiation for posterior fossa brain tumors between January 1990 and December 2001, some of whom underwent prophylactic oophoropexy. Materials and Methods: Fifty-eight consecutive girls who received craniospinal irradiation for a brain tumor were identified through the Harvard Joint Center for Radiation Therapy database. Charts were reviewed. Twenty-six of these girls had undergone laparoscopic oophoropexy (all performed by MRL) prior to radiation, and the remaining 32 patients served as the comparison group. Patients were excluded if they were prepubertal at diagnosis and had not yet reached pubertal age, were lost to follow-up, or had died before pubertal age. In order to insure homogeneity of the group, we also excluded any patient whose primary tumor was located outside of the posterior fossa or who had developed secondary panhypopituitarism. Ovarian failure was defined as an elevated follicle-stimulating hormone level or as prolonged amenorrhea (⬎ 6 months) in girls who had regular menses before radiotherapy. Statistical analyses were performed utilizing the t test for continuous outcomes and Fisher’s exact test for dichotomous outcomes. Results: No surgical complications were reported in the 26 girls (ages 2 to 16 years) who underwent oophoropexy. After applying the above exclusion criteria, 14 patients remained in the oophoropexy group and 11 patients in the control group. All patients underwent both craniospinal radiation therapy and chemotherapy. Mortality rates were similar in both groups before and after exclusions. Mean age at diagnosis, mean length of followup, proportion of patients with high-risk tumors, and mean radiation dose to spine were not statistically different between the two groups. Only one of 14 patients with oophoropexy had ovarian failure versus five of 11 in the control group (P⫽0.056, two-sided).
Conclusions: Oophoropexy may protect against radiation-induced ovarian failure in girls receiving spinal radiation. A high risk (45%) of ovarian failure was seen in girls who received craniospinal radiation and chemotherapy without oophoropexy, similar to risks reported in the literature. In girls who underwent oophoropexy, a lower rate (7%) of ovarian failure was seen. Further follow-up in a larger cohort is planned.
Wednesday, October 15, 2003 4:45 P.M. O-236 Serum Mu¨ llerian inhibiting substance levels in adolescents with anovulatory cycles and normally menstruating girls. Sari Kives, Yong Siow, Sally Perlman, Paige Hertweck, Mary E. Fallat. Univ of Louisville, Louisville, KY. Objective: To compare levels of serum Mu¨ llerian inhibiting substance (MIS), estradiol (E2), free-testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in adolescent girls with anovulatory cycles to levels in normal menstruating girls. Design: A prospective study. Materials and Methods: The study group consisted of twenty-eight girls aged 12 to 17 years with anovulatory cycles (⬎35 days or 21 days) for greater than six months. The control group consisted of 16 girls aged 13 to 19 years with regular menstrual cycles. Blood samples were collected from
Vol. 80, Suppl. 3, September 2003
Wednesday, October 15, 2003 4:15 P.M. O-234 Causes of infertility and ovarian cancer risk. Louise A. Brinton, Emmet J. Lamb, Kamran S. Moghissi, Humberto Scoccia, Carolyn Westhoff, Michelle Althuis. National Cancer Institute, Bethesda, MD; Stanford Univ, Stanford, CA; Wayne State Univ, Detroit, MI; Univ of Illinois at Chicago, Chicago, IL; Columbia Univ, New York, NY. Objective: Evaluation of the risk of ovarian cancer associated with different underlying causes of infertility after adjustment for other risk factors. Design: A standardized algorithm was used to determine causes of infertility from medical records of 12,193 women evaluated between 1965-88 at five clinical sites. Causes were assigned according to the following prioritized scheme: 1) endometriosis, 2) ovulation disorders, 3) tubal disease and pelvic adhesions, 4) male factor or uterine/cervical disorders, and 5) unexplained causes/incomplete work-ups. Follow-up through 1999 via patient questionnaires and linkage against cancer and death registries identified 44 ovarian cancers diagnosed one or more years after first clinic visit. Materials and Methods: Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) compared ovarian cancer risk in the cohort of infertile women to that of U.S. women. Within the study population of infertile women, the different causes of infertility were evaluated by estimating relative risks (RR) of ovarian cancer for different causes of infertility after adjustment for other predictors of risk. Results: Infertile patients were found to be at a significantly high risk of ovarian cancer compared with women in the general population (SIR ⫽ 2.0, 95% CI 1.8-4.0), with the risk higher for patients with primary (SIR ⫽ 2.7) than secondary infertility (SIR ⫽ 1.5). Among infertile women, patients with endometriosis (22% of subjects) were at highest risk of developing ovarian cancer when compared to those with only male factor or uterine/ cervical disorders (14%), with a RR of 1.7 (95% CI 0.6-4.8). This risk was considerably higher than that observed among patients with anovulatory problems (22% of subjects) or tubal disease (16%), who had RRs of only 1.2-1.3. Ovarian cancer risks, however, were higher among patients with primary infertility if causes were attributed to either endometriosis (RR ⫽ 2.3) or tubal disease (RR ⫽ 2.2). In contrast, ovarian cancer risks were elevated among secondary infertility patients diagnosed with anovulatory problems (RR ⫽ 1.7). Subjects with unknown causes or incomplete workups (22%) were also found to be at elevated risk (RR ⫽ 1.8, 95 % CI 0.6-5.1), with no variation according to primary or secondary infertility. The risks associated with different causes of infertility were not changed after adjustment for other ovarian cancer risk factors, including gravidity or parity at follow-up, socioeconomic status, gynecologic operations, oral contraceptive use, and exposure to infertility medications. Conclusion: Determination of ovarian cancer risk should take into account the underlying causes of infertility. Further study of endometriosis in relation to ovarian cancer may provide insights into carcinogenic mechanisms. Supported by: NIH/NCI intramural funding provided through the U.S. government.
Wednesday, October 15, 2003 4:30 P.M. O-235 Ovarian function in pediatric brain cancer survivors after laparoscopic oophoropexy. Wendy Kuohung, Marc R. Laufer, Karen J. Marcus, Debbie
S90
Abstracts
M. Cheng, Lisa R. Diller. Brigham & Women’s Hosp, Boston, MA; Brigham & Women’s Hosp, Children’s Hosp, Boston, MA; Children’s Hosp, Boston, MA; Boston Univ Sch of Public Health, Boston, MA; Dana-Farber Cancer Institute, Boston, MA. Objective: Cancer of the nervous system is the most common solid tumor in children and often is treated with craniospinal radiation after surgical resection. Radiation-induced ovarian failure has been reported to occur in 60% of female cancer survivors receiving spinal radiation. We aimed to determine whether laparoscopic unilateral oophoropexy prior to radiotherapy effectively spares ovarian function from radiation damage. Design: Retrospective analysis of girls aged 16 and younger receiving craniospinal radiation for posterior fossa brain tumors between January 1990 and December 2001, some of whom underwent prophylactic oophoropexy. Materials and Methods: Fifty-eight consecutive girls who received craniospinal irradiation for a brain tumor were identified through the Harvard Joint Center for Radiation Therapy database. Charts were reviewed. Twenty-six of these girls had undergone laparoscopic oophoropexy (all performed by MRL) prior to radiation, and the remaining 32 patients served as the comparison group. Patients were excluded if they were prepubertal at diagnosis and had not yet reached pubertal age, were lost to follow-up, or had died before pubertal age. In order to insure homogeneity of the group, we also excluded any patient whose primary tumor was located outside of the posterior fossa or who had developed secondary panhypopituitarism. Ovarian failure was defined as an elevated follicle-stimulating hormone level or as prolonged amenorrhea (⬎ 6 months) in girls who had regular menses before radiotherapy. Statistical analyses were performed utilizing the t test for continuous outcomes and Fisher’s exact test for dichotomous outcomes. Results: No surgical complications were reported in the 26 girls (ages 2 to 16 years) who underwent oophoropexy. After applying the above exclusion criteria, 14 patients remained in the oophoropexy group and 11 patients in the control group. All patients underwent both craniospinal radiation therapy and chemotherapy. Mortality rates were similar in both groups before and after exclusions. Mean age at diagnosis, mean length of followup, proportion of patients with high-risk tumors, and mean radiation dose to spine were not statistically different between the two groups. Only one of 14 patients with oophoropexy had ovarian failure versus five of 11 in the control group (P⫽0.056, two-sided).
Conclusions: Oophoropexy may protect against radiation-induced ovarian failure in girls receiving spinal radiation. A high risk (45%) of ovarian failure was seen in girls who received craniospinal radiation and chemotherapy without oophoropexy, similar to risks reported in the literature. In girls who underwent oophoropexy, a lower rate (7%) of ovarian failure was seen. Further follow-up in a larger cohort is planned.
Wednesday, October 15, 2003 4:45 P.M. O-236 Serum Mu¨ llerian inhibiting substance levels in adolescents with anovulatory cycles and normally menstruating girls. Sari Kives, Yong Siow, Sally Perlman, Paige Hertweck, Mary E. Fallat. Univ of Louisville, Louisville, KY. Objective: To compare levels of serum Mu¨ llerian inhibiting substance (MIS), estradiol (E2), free-testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in adolescent girls with anovulatory cycles to levels in normal menstruating girls. Design: A prospective study. Materials and Methods: The study group consisted of twenty-eight girls aged 12 to 17 years with anovulatory cycles (⬎35 days or 21 days) for greater than six months. The control group consisted of 16 girls aged 13 to 19 years with regular menstrual cycles. Blood samples were collected from
Vol. 80, Suppl. 3, September 2003