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Papers by Maureen Prewitt

Pediatric Blood & Cancer, 2013

Future fertility is an important concern for many cancer survivors. Cancer therapies have been sh... more Future fertility is an important concern for many cancer survivors. Cancer therapies have been shown to adversely impact reproductive function. However, it is difficult to predict the extent to which reproductive dysfunction will occur. The purpose of this study was to compare measures of ovarian reserve (MOR) and pregnancy rates in young female cancer survivors and similar-aged controls. A prospective cohort study was conducted in a university-hospital setting. Participants were followed annually for a mean 25 months to assess reproductive history, the incidence of pregnancy, and MOR (serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, anti-mullerian hormone (AMH), antral follicle counts and mean ovarian volume). Eighty-four female survivors (average age 26, and 14 years post-treatment) and 98 similar-aged controls that were sexually active with men were included. At baseline, 27/84 survivors and 42/98 controls reported a prior pregnancy. Adjusted models showed that anti-mullerian hormone (AMH) and antral follicle count (AFC) were impaired in survivors with a prior pregnancy compared to controls with a prior pregnancy (P < 0.01, P = 0.03). During follow-up in 56 survivors and 74 controls, 19 pregnancies occurred in survivors and 18 in controls. Comparison of MOR between survivors who became pregnant and controls who became pregnant revealed that AMH and AFC were impaired in survivors (P < 0.05). Compared to survivors who did not become pregnant, survivors who did were older (P < 0.01) and more likely to be cohabitating (P < 0.01), but had similar MOR and exposure to alkylators (P = 0.34). Survivors achieved pregnancy at a rate similar to controls despite impaired MOR.

Journal of Assisted Reproduction and Genetics, 2012

Background As advancements in cancer therapies have led to dramatic improvements in long term sur... more Background As advancements in cancer therapies have led to dramatic improvements in long term survival, there has been increasing interest in methods to expand fertility preservation options for cancer patients. Methods An experimental protocol for ovarian tissue cryopreservation was developed at the University of Pennsylvania for patients requiring gonadotoxic therapies. The protocol for adults was implemented at the Hospital of the University of Pennsylvania and for children at the Children's Hospital of Philadelphia in collaboration with the Oncofertility Consortium and the National Physicians Cooperative (NPC). Results A total of twenty-one patients (age range: 8-36 years) have cryopreserved ovarian tissue as part of this study. While patients had a variety of diagnoses and treatment exposures, 10/ 21 (48 %) patients suffered from hematologic disorders and 43 % were anticipating stem cell transplantation. No patients have requested that the tissue be used for clinical purposes. Conclusions Ovarian tissue cryopreservation protocols can be implemented at pediatric and adult institutions through multi-disciplinary collaboration. While more research is needed to determine the safety and efficacy of ovarian tissue cryopreservation, this procedure provides hope for preserving the ability to have biological offspring to patients facing gonadotoxic therapies for a variety of medical conditions. Capsule A protocol for ovarian tissue cryopreservation has been successfully established at an adult and pediatric hospital through multi-disciplinary collaboration.

Fertility and Sterility, 2012

To determine whether measures of ovarian reserve differ between females exposed to cancer therapi... more To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared with healthy controls of similar age and late reproductive age. Cross-sectional analysis of data from a prospective cohort study. University medical center. Seventy-one cancer survivors aged 15-39 years; 67 healthy, similarly aged unexposed subjects; and 69 regularly menstruating women of late reproductive age (40-52 years). None. Early follicular-phase hormones (FSH, E(2), inhibin B, antimüllerian hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral follicle counts [AFC]) were compared using multivariable linear regression. In adjusted models, FSH, AMH, and AFC differed between exposed vs. unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85 ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors had lower levels of AMH and AFC compared with controls. Alkylating agent dose score was associated with increased levels of FSH and decreased levels of AMH. Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and ovarian volume. Antimüllerian hormone was similar in women previously exposed to high-dose cancer therapy and 40-42-year-old controls. Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared with unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to those in late-reproductive-age women. The predictive value of measures for pregnancy and menopause must be studied. CLINICALTRIALS.GOV IDENTIFIER: NCT01143844.

Fertility and Sterility, 2008

OBJECTIVE: Evidence shows that women from socio-economically disadvantaged backgrounds enter meno... more OBJECTIVE: Evidence shows that women from socio-economically disadvantaged backgrounds enter menopause 1-2 years earlier than their more affluent counterparts. To date, no study has examined whether the socioeconomic conditions of a woman's environment may accelerate the reproductive aging process underlying her entry into menopause. Here, we assessed community socioeconomic status (SES) and neighborhood quality in relation to ovarian aging (indexed by antral follicle count [AFC]) in a sample of reproductive-age women with regular menses. DESIGN: In cross-sectional analyses of a sample derived from the OVA Study, an investigation of the correlates of ovarian aging, the relation between community SES and AFC was evaluated in the full sample (n¼310; ages 25-45; 65% Caucasian) and the relation between neighborhood quality and AFC was evaluated in a representative subsample (n¼152).

Fertility and Sterility, 2009

ABSTRACT The purpose of the study is to assess the quality-of-life scores and possible associatio... more ABSTRACT The purpose of the study is to assess the quality-of-life scores and possible association with measures of ovarian reserve in female cancer survivors compared to healthy controls of similar age. In this prospective cohort study, fifty-nine cancer survivors aged 16-39 years and 66 healthy, similarly aged unexposed women were recruited at the University of Pennsylvania. The primary outcome measures are the generic and cancer-specific domain scores on the Quality of Life in Adult Cancer Survivors (QLACS) instrument, early follicular phase serum hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), inhibin B (INH), anti-Mullerian hormone (AMH), and ovarian ultrasound measurements [ovarian volume and antral follicle count (AFC)]. Cancer survivors had significantly higher total and cancer-specific domain scores compared to unexposed participants. Serum AMH, INH, ovarian volume, and AFC were lower while serum FSH was higher in cancer survivors. Although survivors exhibited diminished ovarian reserve, these markers were not independently associated with total QLACS score. Cancer survivors with irregular menstrual function were found to have lower quality-of-life (QOL) scores than those with regular cycles. We found that QOL appears to be significantly impaired in cancer survivors compared to controls, even when remote from initial cancer diagnosis. In addition, our study suggests that reproductive aging contributes to QOL in the setting of irregular menses and likely profound impairment of ovarian function.

Fertility and Sterility, 2012

Objective: To determine the exact nature and timing of alterations in thyroid function throughout... more Objective: To determine the exact nature and timing of alterations in thyroid function throughout controlled ovarian hyperstimulation (COH). Design: Prospective cohort study. Setting: University fertility clinic. Patient(s): Fifty-seven women undergoing COH as part of planned in vitro fertilization. Intervention(s): None. Main Outcome Measure(s): Timing and magnitude of change in serum thyroid hormones, including TSH, total and free T 4 , E 2 , and thyroxine-binding globulin (TBG), measured at six time points from before stimulation to 2 weeks after serum pregnancy test. Result(s): Geometric mean serum TSH increased during stimulation, peaking 1 week after hCG administration compared with baseline (2.44 vs. 1.42 mIU/L), as did free T 4 (1.52 vs. 1.38 ng/dL) and TBG (32.86 vs. 21.52 mg/mL). Estradiol levels increased, peaking at hCG administration (1743.21 vs. 71.37 pg/mL). Of 50 women with baseline TSH %2.5 mIU/L, 22 (44.0%) had a subsequent rise in TSH to >2.5 during or after COH. The pattern of change over time in TSH concentrations was significantly influenced by baseline hypothyroidism and whether pregnancy was achieved. Conclusion(s): COH led to significant elevations in TSH, often above pregnancy appropriate targets. These findings were particularly evident in women with preexisting hypothyroidism and may have important clinical implications for screening and thyroid hormone supplementation. (Fertil Steril Ò 2012;97:585-91.

Fertility and Sterility, 2010

Fertility and Sterility, 2013

Objective-To identify factors associated with ovarian reserve (OR) impairment during and immediat... more Objective-To identify factors associated with ovarian reserve (OR) impairment during and immediately after chemotherapy.

Pediatric Blood & Cancer, 2013

Future fertility is an important concern for many cancer survivors. Cancer therapies have been sh... more Future fertility is an important concern for many cancer survivors. Cancer therapies have been shown to adversely impact reproductive function. However, it is difficult to predict the extent to which reproductive dysfunction will occur. The purpose of this study was to compare measures of ovarian reserve (MOR) and pregnancy rates in young female cancer survivors and similar-aged controls. A prospective cohort study was conducted in a university-hospital setting. Participants were followed annually for a mean 25 months to assess reproductive history, the incidence of pregnancy, and MOR (serum follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin B, anti-mullerian hormone (AMH), antral follicle counts and mean ovarian volume). Eighty-four female survivors (average age 26, and 14 years post-treatment) and 98 similar-aged controls that were sexually active with men were included. At baseline, 27/84 survivors and 42/98 controls reported a prior pregnancy. Adjusted models showed that anti-mullerian hormone (AMH) and antral follicle count (AFC) were impaired in survivors with a prior pregnancy compared to controls with a prior pregnancy (P < 0.01, P = 0.03). During follow-up in 56 survivors and 74 controls, 19 pregnancies occurred in survivors and 18 in controls. Comparison of MOR between survivors who became pregnant and controls who became pregnant revealed that AMH and AFC were impaired in survivors (P < 0.05). Compared to survivors who did not become pregnant, survivors who did were older (P < 0.01) and more likely to be cohabitating (P < 0.01), but had similar MOR and exposure to alkylators (P = 0.34). Survivors achieved pregnancy at a rate similar to controls despite impaired MOR.

Journal of Assisted Reproduction and Genetics, 2012

Background As advancements in cancer therapies have led to dramatic improvements in long term sur... more Background As advancements in cancer therapies have led to dramatic improvements in long term survival, there has been increasing interest in methods to expand fertility preservation options for cancer patients. Methods An experimental protocol for ovarian tissue cryopreservation was developed at the University of Pennsylvania for patients requiring gonadotoxic therapies. The protocol for adults was implemented at the Hospital of the University of Pennsylvania and for children at the Children's Hospital of Philadelphia in collaboration with the Oncofertility Consortium and the National Physicians Cooperative (NPC). Results A total of twenty-one patients (age range: 8-36 years) have cryopreserved ovarian tissue as part of this study. While patients had a variety of diagnoses and treatment exposures, 10/ 21 (48 %) patients suffered from hematologic disorders and 43 % were anticipating stem cell transplantation. No patients have requested that the tissue be used for clinical purposes. Conclusions Ovarian tissue cryopreservation protocols can be implemented at pediatric and adult institutions through multi-disciplinary collaboration. While more research is needed to determine the safety and efficacy of ovarian tissue cryopreservation, this procedure provides hope for preserving the ability to have biological offspring to patients facing gonadotoxic therapies for a variety of medical conditions. Capsule A protocol for ovarian tissue cryopreservation has been successfully established at an adult and pediatric hospital through multi-disciplinary collaboration.

Fertility and Sterility, 2012

To determine whether measures of ovarian reserve differ between females exposed to cancer therapi... more To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared with healthy controls of similar age and late reproductive age. Cross-sectional analysis of data from a prospective cohort study. University medical center. Seventy-one cancer survivors aged 15-39 years; 67 healthy, similarly aged unexposed subjects; and 69 regularly menstruating women of late reproductive age (40-52 years). None. Early follicular-phase hormones (FSH, E(2), inhibin B, antimüllerian hormone [AMH]) and ovarian ultrasound measurements (ovarian volume and antral follicle counts [AFC]) were compared using multivariable linear regression. In adjusted models, FSH, AMH, and AFC differed between exposed vs. unexposed subjects (FSH 11.12 mIU/mL vs. 7.25 mIU/mL; AMH 0.81 ng/mL vs. 2.85 ng/mL; AFC 14.55 vs. 27.20). In participants with an FSH <10 mIU/mL, survivors had lower levels of AMH and AFC compared with controls. Alkylating agent dose score was associated with increased levels of FSH and decreased levels of AMH. Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC, and ovarian volume. Antimüllerian hormone was similar in women previously exposed to high-dose cancer therapy and 40-42-year-old controls. Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared with unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to those in late-reproductive-age women. The predictive value of measures for pregnancy and menopause must be studied. CLINICALTRIALS.GOV IDENTIFIER: NCT01143844.

Fertility and Sterility, 2008

OBJECTIVE: Evidence shows that women from socio-economically disadvantaged backgrounds enter meno... more OBJECTIVE: Evidence shows that women from socio-economically disadvantaged backgrounds enter menopause 1-2 years earlier than their more affluent counterparts. To date, no study has examined whether the socioeconomic conditions of a woman's environment may accelerate the reproductive aging process underlying her entry into menopause. Here, we assessed community socioeconomic status (SES) and neighborhood quality in relation to ovarian aging (indexed by antral follicle count [AFC]) in a sample of reproductive-age women with regular menses. DESIGN: In cross-sectional analyses of a sample derived from the OVA Study, an investigation of the correlates of ovarian aging, the relation between community SES and AFC was evaluated in the full sample (n¼310; ages 25-45; 65% Caucasian) and the relation between neighborhood quality and AFC was evaluated in a representative subsample (n¼152).

Fertility and Sterility, 2009

ABSTRACT The purpose of the study is to assess the quality-of-life scores and possible associatio... more ABSTRACT The purpose of the study is to assess the quality-of-life scores and possible association with measures of ovarian reserve in female cancer survivors compared to healthy controls of similar age. In this prospective cohort study, fifty-nine cancer survivors aged 16-39 years and 66 healthy, similarly aged unexposed women were recruited at the University of Pennsylvania. The primary outcome measures are the generic and cancer-specific domain scores on the Quality of Life in Adult Cancer Survivors (QLACS) instrument, early follicular phase serum hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), inhibin B (INH), anti-Mullerian hormone (AMH), and ovarian ultrasound measurements [ovarian volume and antral follicle count (AFC)]. Cancer survivors had significantly higher total and cancer-specific domain scores compared to unexposed participants. Serum AMH, INH, ovarian volume, and AFC were lower while serum FSH was higher in cancer survivors. Although survivors exhibited diminished ovarian reserve, these markers were not independently associated with total QLACS score. Cancer survivors with irregular menstrual function were found to have lower quality-of-life (QOL) scores than those with regular cycles. We found that QOL appears to be significantly impaired in cancer survivors compared to controls, even when remote from initial cancer diagnosis. In addition, our study suggests that reproductive aging contributes to QOL in the setting of irregular menses and likely profound impairment of ovarian function.

Fertility and Sterility, 2012

Objective: To determine the exact nature and timing of alterations in thyroid function throughout... more Objective: To determine the exact nature and timing of alterations in thyroid function throughout controlled ovarian hyperstimulation (COH). Design: Prospective cohort study. Setting: University fertility clinic. Patient(s): Fifty-seven women undergoing COH as part of planned in vitro fertilization. Intervention(s): None. Main Outcome Measure(s): Timing and magnitude of change in serum thyroid hormones, including TSH, total and free T 4 , E 2 , and thyroxine-binding globulin (TBG), measured at six time points from before stimulation to 2 weeks after serum pregnancy test. Result(s): Geometric mean serum TSH increased during stimulation, peaking 1 week after hCG administration compared with baseline (2.44 vs. 1.42 mIU/L), as did free T 4 (1.52 vs. 1.38 ng/dL) and TBG (32.86 vs. 21.52 mg/mL). Estradiol levels increased, peaking at hCG administration (1743.21 vs. 71.37 pg/mL). Of 50 women with baseline TSH %2.5 mIU/L, 22 (44.0%) had a subsequent rise in TSH to >2.5 during or after COH. The pattern of change over time in TSH concentrations was significantly influenced by baseline hypothyroidism and whether pregnancy was achieved. Conclusion(s): COH led to significant elevations in TSH, often above pregnancy appropriate targets. These findings were particularly evident in women with preexisting hypothyroidism and may have important clinical implications for screening and thyroid hormone supplementation. (Fertil Steril Ò 2012;97:585-91.

Fertility and Sterility, 2010

Fertility and Sterility, 2013

Objective-To identify factors associated with ovarian reserve (OR) impairment during and immediat... more Objective-To identify factors associated with ovarian reserve (OR) impairment during and immediately after chemotherapy.