What do women with cancer need to make decisions about fertility preservation?

Internal consistencies of the overall RCAC-male scale and six subscales

Mean score (SD)

Cronbach’s alpha

2.89 (0.77) 2.90 (1.32) 2.74 (1.15) 3.43 (1.23) 2.85 (1.06) 2.96 (1.13) 2.28 (1.00)

0.88 0.92 0.80 0.89 0.74 0.86 0.80

RCAC-male Fertility potential Partner disclosure Child’s health Personal health Acceptance Achieving pregnancy

Note: Higher scores indicate greater concern. Response scales range 1-5. OBJECTIVE: To measure the reproductive concerns of young adult male cancer survivors. DESIGN: Mixed methods. MATERIALS AND METHODS: In phase I, 10 young adult male cancer survivors, age 18-35 years, participated in a telephone interview. Prior to the interview, they received a version of the 18-item Reproductive Concerns After Cancer (RCAC) scale that was originally validated for females, with language adapted for males based on expert opinion. The RCAC scale includes six domains of concern (fertility potential, partner disclosure, child’s health, personal health, acceptance, becoming pregnant). During the interview, participants were asked to critically appraise each item using a verbal probing technique. They were also asked about overall structure of the survey, cultural sensitivity and relevance. In Phase II, we are recruiting young adult male cancer survivors to a web-based survey testing the resultant RCAC-male scale. We calculated internal consistency of the scale and six subscales as coefficient alpha. RESULTS: Phase I interviews provided feedback to refine item wording and evidence of face validity, and resulted in an 18-item RCAC-male scale that includes six domains in parallel with the original RCAC scale for females. As of April 2017, 40 participants had completed the survey with the adapted scale. Participants had a mean age of 29.4 years (SD 4.7), 73% were college graduates, and 61% had a committed partner. The most common cancers were hematologic (34%), thyroid (22%) and testicular (10%). Similar to the original RCAC scale, internal consistencies for the overall RCAC-male scale and the six subscales were in the acceptable to good range. CONCLUSIONS: Feedback from young adult male cancer survivors supported the face validity of the RCAC-male scale. Preliminary data suggest that the scale and subscales have acceptable internal consistency, providing support for the scale’s reliability. A larger sample size is needed to provide evidence of validity. This scale has potential to be an effective tool to identify young adult male cancer survivors’ concerns related to fertility and parenthood and to assist with meeting their long-term reproductive health needs. https://health.ucsd.edu/ specialties/cancer/programs/fertility/Pages/research.aspx Supported by: ACS grant #120500-PFT-11-008-01-CPPB, UCSD Academy of Clinican Scholars.

P-206 Tuesday, October 31, 2017 GNRHA CO-TREATMENT DOES NOT PREVENT CHEMOTHERAPY-INDUCED PRIMORDIAL FOLLICLE LOSS AND DNA DAMAGE. E. Taylan,a Y. Sugishita,b T. Kawahara,c K. H. Oktay.d aObstetrics and Gynecology, New York Medical College, Valhalla, NY; bNew York Medical College, Valhalla, NY; cOBGYN, White Plains, NY; dObstetrics & Gynecology, NY Medical College, Valhalla, NY. OBJECTIVE: There has been an ongoing controversy regarding the effectiveness of GnRH analogs in preserving ovarian function against

chemotherapy-induced damage. We conducted this animal study to determine whether co-administration of a GnRHa would prevent cyclophosphamide (Cy)-induced primordial (pdf) and primary follicle (pyf) oocyte death and DNA damage. DESIGN: Experimental animal study. MATERIALS AND METHODS: After unilateral oophorectomy, 4-wk-old FVB mice were given daily intraperitoneal injection of 200 mg/ kg Cyclophosphamide (Cy) either alone for 3 days (n¼4) or with 250 mg/ kg Goserelin (n¼4) starting 3 days prior and continuing the duration of chemotherapy. The remaining ovary was harvested at the end of chemotherapy. Ovaries were fixed and serially sectioned at 5 mm, and every 10th section was studied. Pdf and pyf follicle densities, oocyte DNA double strand breaks (by gH2AX) and apoptotic cell death pathway activation (AC3) were determined by immunohistochemistry and compared between the pre- and post-chemo ovaries of each mice in a paired analysis, as well as between the two arms post-chemo. RESULTS: Results are summarized in table-1. In both the Cy-only and Cy+GnRHa groups, pdf and pyf densities declined significantly compared to pre-chemo (p¼ 0.003 and 0.001, respectively). However, there was no difference between the post-chemo follicle densities of the two groups. Likewise, both Cy and Cy+GnRHa resulted in significantly increased follicular DNA damage and apoptotic death (p<0.01) compared to baseline readings. However, post-chemo incidences of follicle oocyte DNA damage and apoptotic death were similar between the Cy and Cy+GnRHa groups. CONCLUSIONS: This animal study shows that GnRHa co-treatment does not prevent chemotherapy-induced damage to ovarian reserve. Taken together with recent clinical data, ovarian suppression via GnRHamay not be recommended for fertility preservation. Supported by: 5R01HD053112-05 P-207 Tuesday, October 31, 2017 WHAT DO WOMEN WITH CANCER NEED TO MAKE DECISIONS ABOUT FERTILITY PRESERVATION? T. L. Woodard,a,b A. S. Hoffman,c L. Covarrubias,d A. Mathur,e A. Bradford,f R. J. Volk.c aGynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; bObstetrics and Gynecology, Baylor College of Medicine, Houston, TX; cHealth Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX; dThe University of Texas MD Anderson Cancer Center, Houston, TX; eMD Anderson Cancer Research Center, Houston, TX; fBaylor College of Medicine, Houston, TX. OBJECTIVE: As the number of cancer survivors increases, the burden of cancer-related infertility is becoming more recognized. Little is known about the optimal way to provide fertility preservation decision-making support during the stressful period of time between diagnosis and initiation of cancer treatment. In preparation for developing a patient decision aid, this study assessed informational and decisionmaking needs of women diagnosed with cancer. DESIGN: Qualitative study using thematic analysis MATERIALS AND METHODS: Semi-structured interviews with 28 female cancer survivors assessed women’s experiences with fertilityrelated decision making during their cancer care, decision-making needs, and barriers and facilitators to potential interventions. Thematic analysis identified 3 primary informational needs and 15 potential key decision-making factors. A focus group of 8 additional female cancer survivors and a stakeholder advisory panel reviewed, ranked, and refined these information and decision-making needs to identify priority concepts and delivery strategies.

TABLE 1. Efficacy of GnRHa in Preventing Chemotherapy-Induced Follicle Death and DNA Damage

Variables Pdf Density (/mm3) gH2AX+ Pdf (%) AC3+ Pdf (%) Pyf Density (/mm3) gH2A+ Pyf (%) AC3+ Pyf (%)

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Pre-chemo

Cy

Cy+GnRHa

Cy vs. Pre-chemo

Cy+GnRHa vs. Pre-chemo

Cy vs. Cy+GnRHa

1,30025.8 12.30.08 0 1,400163.3 15.40.1 0

685128.4 71.26.9 53.60.6 85075.9 75.64.8 58.60.13

640121.3 755.8 38.10.06 82083.6 72.86.4 46.80.04

<0.01 <0.01 <0.01 <0.01 <0.01 <0.01

<0.01 <0.01 <0.01 <0.01 <0.01 <0.01

0.8 0.69 0.78 0.94 0.74 0.75

ASRM Abstracts

Vol. 108, No. 3, Supplement, September 2017

RESULTS: Women identified 3 primary informational needs: clear, concise information about fertility risk; fertility preservation options including their risks and costs; and additional methods of achieving parenthood after treatment. They also requested information in a format they could access on their own at their convenience, summarized in tables where possible, and tailored to their cancer type. Many requested testimonials from former patients or links to survivor groups, as well guidance in how to seek a referral to a fertility preservation specialist. CONCLUSIONS: Women with cancer report significant knowledge gaps about fertility and alternative parenthood options, as well as difficulty finding timely and trustworthy information. Interventions to address these needs should tailor information by cancer type and may be optimally delivered in broadly accessible and flexible formats (e.g. websites or multimedia). Supported by: This work was supported by funding from the Duncan Family Institute for Cancer Prevention and Risk Assessment.

parents’ decisions (Table 1). The desire for genetically-related children also drove patients’ decisions (93.3%), but only 26.7% considered the stress of infertility. All refusers thought OTC was a somewhat good idea and desired for their daughters to have genetically-related children, but risks of the biopsy and desire not to complicate treatment (40% and 66.7%, respectively) drove their decisions. All respondents felt in control of their decision and levels of mood disturbance were similar. CONCLUSIONS: OTC is a promising option for prepubertal females and young women facing imminent gonadotoxic therapy. Though the decision to undergo OTC is difficult and often urgent, this study suggests that parents and patients can carefully weigh the risks and benefits and make an informed decision during these critical times. It is reasonable to offer OTC to prepubertal females and young women prior to gonadotoxic therapy. Supported by: Children’s Hospital of Philadelphia Department of Pediatrics Chair’s Initiative.

P-208 Tuesday, October 31, 2017

P-209 Tuesday, October 31, 2017

OVARIAN TISSUE CRYOPRESERVATION (OTC) IN PREPUBERTAL GIRLS AND YOUNG WOMEN: AN ANALYSIS OF PARENTS’ AND PATIENTS’ DECIC. Carlson,b SION-MAKING. C. Sullivan-Pyke,a M. Prewitt,a C. Gracia,a J. Ginsberg.b aUniversity of Pennsylvania, Philadelphia, PA; bDivision of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA.

ASSOCIATION OF GERMLINE BRCA MUTATIONS WITH IMPAIRED FERTILITY PRESERVATION CYCLE OUTCOMES. V. Turan,a F. Moy,b K. H. Oktay.c aObstetrics & Gynecology, Yeni Yuzyil University School of Medicine, Istanbul, Turkey; bPathology, New York Medical College, Valhalla, NY; cObstetrics & Gynecology, NY Medical College, Valhalla, NY.

OBJECTIVE: Survival rates for childhood cancer have dramatically increased due to advances in therapy, however, infertility often results from treatment. Experimental OTC may help prepubertal females and young women preserve their fertility. The purpose of this study was to explore the decision-making influences, perceived level of control over decision-making, and mood-states of patients and parents who were offered OTC prior to gonadotoxic therapy. DESIGN: Retrospective cohort. MATERIALS AND METHODS: Parents of patients planning to undergo gonadotoxic therapy who were offered OTC prior to therapy were asked to complete questionnaires regardless of whether they elected OTC. Patients who were at least 12 years old were also asked to complete questionnaires. Two validated instruments were also used: The Decision-Making Control Instrument (DCMI) as a measure of the strength of control in decision-making and the Profile of Mood States (POMS) to describe mood states when faced with their decision. The factors that influenced decision-making were compared using Student’s t test, and the scores of DCMI and POMS were compared using the Wilcoxon rank sum test. RESULTS: Thirty-six parents and 15 patients who underwent OTC completed questionnaires. Five parents who declined OTC also completed questionnaires. Most accepters thought OTC was a good idea (72.2% parents; 73.3% patients) and that in future, science would enable the use of cryopreserved ovarian tissue to restore fertility (77.8% parents; 60% patients). The desire for genetically-related children (86.7%) and prevention of the stress of infertility (66.7%) drove

OBJECTIVE: Recent data suggest that women with BRCA mutations may have diminished ovarian reserve1. However, it is not known whether the presence of BRCA mutations affects fertility preservation (FP) cycle outcomes. In this study, we analyzed the impact of BRCA mutations on FP cycle outcomes of patients undergoing ovarian stimulation with an antagonist protocol. DESIGN: The data were generated by the secondary analysis of a prospective database of all females diagnosed with breast cancer who underwent embryo or oocyte cryopreservation for FP. We excluded patients >40 years of age and those who were infertile, had a history of ovarian surgery, or prior exposure to chemotherapy or radiotherapy. MATERIALS AND METHODS: We analyzed 118 patients of which 21 were BRCA-mutation-positive and 97 were BRCA-mutation-negative or -untested. All were stimulated with an antagonist protocol using letrozole combined with rFSH. A multivariate regression analysis was performed to adjust for age and body mass index (BMI). RESULTS: Starting and total gonadotropin doses did not differ between BRCA mutation carriers and those negative or untested (Starting dose: 242.8  64.4 vs. 256.5  94.5 IU; p¼0.433 and total dose: 1,905.0  883.5 vs. 2,208.1  1175.1 IU; p¼0.109 respectively). Women with BRCA mutations produced fewer oocytes (16.4  7.7 vs 11.0  8.0, p¼0.015) and embryos (8.2  4.7 vs. 5.1  4.4, p¼0.013) compared to those who were BRCA negative or untested. After adjusting for age and BMI, these differences became more prominent with marginally lower fertilization rates in women with BRCA mutations (Table 1).

Parental Decision-Making Influences

Decision-making Influences Religious beliefs Family opinion Desire for genetically related children Prevent psychological distress of infertility Moral objections to assisted reproductive technology Financial implications Limited time to decide Lack of knowledge Desire to not complicate treatment Risks of the procedure Experimental nature of procedure

FERTILITY & STERILITYÒ

A lot (%)

A moderate amount (%)

A little bit (%)

Not at all (%)

11.1 27.8 88.9 66.7 8.3

5.6 13.9 2.8 19.4 8.3

5.6 25.0 5.6 11.1 8.3

77.8 33.3 2.8 2.8 75.0

13.9 11.1 5.6 19.4 2.9 8.3

0 13.9 5.6 8.3 22.9 13.9

8.3 11.1 16.7 30.6 20.0 25.0

75.0 63.9 72.2 41.7 54.3 52.8

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