- Email: [email protected]
Letrozole supplementation during ovarian stimulation alters oocyte maturation rates in breast cancer candidates for fertility preservation
TABLE 1. Clinical outcomes according to pre- and post-vitrification-warming morphology
CHANGE IN MORPHOLOGICAL GRADE IMPROVE (n¼509) DOWNGRADE (n¼169) Implantation Clinical pregnancy Early pregnancy loss ICM
57.8%* (294/509) 54.2%* (276/509) 15.5% (79/509) IMPROVE (n¼109)
Implantation Clinical pregnancy Early pregnancy loss TROPHECTODERM
60.6%*+ (66/109) 56.9%*+ (62/109) 14.7% (16/109) IMPROVE (n¼56)
Implantation Clinical pregnancy Early pregnancy loss
64.3%* (36/56) 58.9%* (33/56) 19.6% (11/56)
49.7%*+ (84/169) 46.2%*+ (78/169) 18.9% (32/169) DOWNGRADE (n¼61)
COULD NOT ASSESS (n¼37)
43.2%o (16/37) 40.5%o (15/37) 21.6% (8/37) COULD NOT ASSESS (n¼49) o o^ 34.4%* (21/61) 61.0% (1102/1807) 40.8%+^ (20/49) 32.8%+o (20/61) 56.4%o^ (1019/1807) 36.7%*^ (18/49) 22.9% (14/61) 16.8% (303/1807) 24.5% (12/49) DOWNGRADE (n¼248) SAME (n¼1669) COULD NOT ASSESS (n¼49) 60.6%+ (1012/1669) 40.8%*+o (20/49) 56.0%o (139/248) 56.1%+ (937/1669) 36.7%*+o (18/49) 52.0%o (129/248) 16.1% (40/248) 16.8% (280/1669) 24.5% (12/49)
CONCLUSIONS: Dynamic changes in morphology may provide insight into an embryo’s ability to recover from the microenvironmental stress of vitrification-warming. A downgraded ICM conferred a negative prognosis, whereas a downgraded TE did not impact clinical outcome. Implantation failure and early pregnancy loss increased after transfer of warmed blastocysts whose ICM and TE could not be graded due to delayed reexpansion. These results suggest that rapid recovery and re-expansion after warming is associated with superior developmental competence and may serve as a clinical marker of embryo quality. P-186 Tuesday, October 31, 2017 LONG TERM CO-TRANSPLANTATION OF HUMAN OVARIAN TISSUE WITH AMH-PRODUCING ENDOTHELIAL CELLS INCREASE PRODUCTIVITY AND LONGEVITY OF THE GRAFT. L. Man, R. Bodine, L. Park, N. Zaninovic, G. L. Shatmann, Z. Rosenwaks, D. James. CRMI Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, NYC, NY. OBJECTIVE: A major obstacle to salvaging a robust pool of functional follicles from cryopreserved ovarian tissue following auto-transplantation is the global activation of the follicular pool that occurs during the ischemic window. AMH has been suggested to exert a repressive input on activation and/or growth of follicles during normal folliculogenesis. We used lentivirus to engineer exogenous endothelial cells (exECs) to constitutively express and secrete AMH, aiming to reduce premature follicular mobilization and growth upon co-transplantation in long-term grafts. DESIGN: Xenograft of human ovarian tissue into NSG mice with cotransplantation of ECs, and ECs ectopically expressing human AMH. MATERIALS AND METHODS: In order to consolidate the phenomenon of activation, despite co-transplantation with ECs, we co-transplanted multiple grafts from a single patient and harvested at 2 (n¼3), 3 (n¼4), and 14 (n¼2) weeks. Also, ECs were transduced with lentiviral vectors linked to a fluorescent reporter gene (mCherry) expressing AMH. Human ovarian tissue was co-transplanted with AMH-ECs into NSG oophorectomized mice (n¼2); as controls, we co-transplanted patient-matched ovarian tissue with ECs (n¼2). Engrafted tissue was harvested 14 weeks after transplantation. The ratio of follicles in each treatment was assessed in histologic sections using light and confocal microscopy. RESULTS: Control grafts harvested at 2, 3 and 14 weeks revealed a shift in the follicular pool away from quiescence with a decreased percentage of primordial follicles upon increased graft length. In contrast, grafts co-transplanted with AMH-ECs showed a significant retention of primordial follicles at 14 weeks. In these long-term grafts, we found a 4.6-fold increase in primordial follicles percentage with AMH-ECs; 18.390.75 vs. blankECs 3.991.61, P¼0.01. For primary follicles, we found a reverse ratio, an approximately 0.8-fold decrease compared to blank-ECs; 33.403.28 vs. 41.941.30 respectively, P¼0.05. CONCLUSIONS: Engineered exECs that constitutively express AMH induced a greater proportion of quiescent primordial follicles relative to control exECs, indicating suppression of premature mobilization that has been noted in the context of ovarian tissue transplantation. These findings present
FERTILITY & STERILITYÒ
SAME (n¼1176) 62.8%+o (738/1176) 57.7%+o (679/1176) 17.3% (203/1176) SAME (n¼1807)
P value *0.067 +0.001 o0.015 *0.068 o0.037 +0.0046 NS P value *0.001 +0.02 o<0.0001 ^0.004 *0.019 +0.003 o 0.0002 ^0.006 NS P value *0.016 +0.005 o0.05 *0.02 +0.007 o0.05 NS
a cell-based strategy that combines accelerated perfusion with a direct paracrine delivery of a bioactive payload to transplanted ovarian tissue. Improved tissue viability and enforced retention of a quiescent primordial follicle pool combine to increase productivity and longevity of ovarian tissue grafts. References: 1. Aubard, Y., Piver, P., Cogni, Y., Fermeaux, V., Poulin, N., and Driancourt, M.A. (1999). Orthotopic and heterotopic autografts of frozenthawed ovarian cortex in sheep. Hum Reprod 14, 2149-2154. 2. Baird, D.T., Webb, R., Campbell, B.K., Harkness, L.M., and Gosden, R.G. (1999). Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C. Endocrinology 140, 462-471. 3. Newton, H., Aubard, Y., Rutherford, A., Sharma, V., and Gosden, R. (1996). Low temperature storage and grafting of human ovarian tissue. Hum Reprod 11, 1487- 1491. 4. Van Eyck, A.S., Jordan, B.F., Gallez, B., Heilier, J.F., Van Langendonckt, A., and Donnez, J. (2009). Electron paramagnetic resonance as a tool to evaluate human ovarian tissue reoxygenation after xenografting. Fertil Steril 92, 374-381. 5. Dolmans, M.M., Martinez-Madrid, B., Gadisseux, E., Guiot, Y., Yuan, W.Y., Torre, A., Camboni, A., Van Langendonckt, A., and Donnez, J. (2007). Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice. Reproduction 134, 253-262. 6. Amorim, C.A., David, A., Dolmans, M.M., Camboni, A., Donnez, J., and Van Langendonckt, A. (2011). Impact of freezing and thawing of human ovarian tissue on follicular growth after long-term xenotransplantation. J Assist Reprod Genet 28, 1157-1165. 7. Kawamura, K., Cheng, Y., Suzuki, N., Deguchi, M., Sato, Y., Takae, S., Ho, C.H., Kawamura, N., Tamura, M., Hashimoto, S., et al. (2013). Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A 110, 17474-17479. 8. Suzuki, N., Yoshioka, N., Takae, S., Sugishita, Y., Tamura, M., Hashimoto, S., Morimoto, Y., and Kawamura, K. (2015). Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod 30, 608-615. Supported by: Supported by: Internal (CRMI funding). P-187 Tuesday, October 31, 2017 LETROZOLE SUPPLEMENTATION DURING OVARIAN STIMULATION ALTERS OOCYTE MATURATION RATES IN BREAST CANCER CANDIDATES FOR FERTILITY PRESERVATION. M. Grynberga C. Sonigo.b aDepartment of Reproductive Medicine and Fertility Preservation, H^opital Jean Verdier, Bondy, France; bDepartment of Reproductive Medicine, Jean Verdier Hospital, Bondy, France. OBJECTIVE: Oocyte and/or embryo vitrification after controlled ovarian stimulation (COS) represents the most established and efficient method of female fertility preservation (FP) before cancer treatment. However, traditional COS regimens are associated with supraphysiologic serum estradiol and are therefore not recommended in estrogen-sensitive diseases such as breast
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cancer (BC). As a result, specific protocol using aromatase inhibitors (letrozole) were developed. The present investigation aimed to investigate whether COS with letrozole supplementation (COSTLES) modifies ovarian response and follicle responsiveness to exogenous FSH in BC patients? DESIGN: Prospective study. MATERIALS AND METHODS: This is the first investigation comparing COSTLES and standard ovarian stimulation in BC patients. We studied 133 BC patients, 25 to 40 years of age, candidates for FP using oocyte and/or embryo vitrification following COS. Of these, 68 patients underwent COSTLES while 65 had standard GnRH antagonist protocol. All women had 2 ovaries, no history of chemotherapy, BMI<30 Kg/m2 and a breast tumor that was surgically removed. Serum anti-M€ ullerian (AMH) levels and antral follicle count (AFC) were systematically assessed before exogenous FSH administration (d0). Follicle responsiveness to FSH was estimated by the Follicular Output Rate (FORT) calculated from the ratio between the pre-ovulatory follicle count (PFC, 16-20 mm) on the day of oocyte triggering (dOT) and the d0 AFC. RESULTS: Women in the COSTLES and control groups were comparable in terms of age 33.44.7 vs. 33.83.5 years, respectively), BMI (21.63.1 vs. 22.62.4 Kg/m2) and ovarian reserve tests (AMH: 2.21.8 vs. 2.72.3ng/mL; AFC: 18.510.5 vs. 17.910.7 follicles). After comparable starting doses and total amount of exogenous FSH (30461332 vs. 29961344IU, respectively), the FORT index did not differ significantly between groups (33.824.6 vs. 37.219.8%, respectively), leading to a similar number of oocyte recovered (12.38.3 vs. 12.58.7 oocytes, respectively). However, oocyte maturation rates were significantly lower in COSTLES compared to standard protocol (67.319.7 vs. 76.320.1%, p<0.02). As a result, the number of metaphase 2 oocyte vitrified was lower in patients having received letrozole supplementation (8.12.6 vs. 9.63.4 oocytes, p<0.05 respectively). CONCLUSIONS: Despite similar response to exogenous FSH, BC patients having undergone COSTLES showed reduced oocyte maturation rates in comparison with those having received standard stimulation regimen. At present, there is no evidence that standard COS promotes the proliferation of residual tumoral cells following breast surgery. If not, the confirmation of our results would lead reconsidering the real interest of COSTLES before adjuvant chemotherapy. P-188 Tuesday, October 31, 2017 GONADOTROPIN-RELEASING HORMONE ANALOGS FOR GONADAL PROTECTION DURING GONADOTOXIC CHEMOTHERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS. N. Sofiyeva,a,b T. Siepmann,b,c K. Barlinn,c B. Ata,d E. Seli.a aYale University, New Haven, CT; bCenter for Clinical Research and Management Education, Dresden International University, Dresden, Germany; cDepartment of Neurology, University Hospital Carl Gustav Carus, Technische Universit€at Dresden, Dresden, Germany; dObstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey. OBJECTIVE: To investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents. DESIGN: A systematic review and meta-analysis of randomized and nonrandomized controlled trials. MATERIALS AND METHODS: Major databases, systematic snowballing, registered ongoing trials were used for data extraction. Studies published prior to March 2017 were assessed. Studies conducted in reproductive-aged women (<45 years) with a study group (co-administration of GnRHa) and control group (chemotherapy without GnRHa) were included in the analysis. There was no restriction for publication language. Studies were excluded if participants were given estrogen and/or progesterone, or pelvic radiotherapy. The outcome measure was the resumption of menstruation. Statistical analyses were performed with STATA 14.2. RESULTS: The database search yielded 25,151 citations and 80 manuscripts were assessed as full-text. Nineteen studies (12 RCTs and 7 Cohort studies) published between 1987 and 2015 were included in the quantitative analysis, revealing a significant protective effect of GnRHa (n¼1,106; RR:1.36; CI:1.151.61), although with high heterogeneity (I2¼82.2%). In subgroup analysis, a significant difference was detected in favor of GnRH co-treatment both in RCTs and cohort studies (RR:1.32; CI:1.06-1.64 and RR:1.42; CI:1.09-1.86, respectively). A significant benefit of GnRHa was approved in all subgroups by the underlying disease, i.e. breast cancer, autoimmune diseases, hematological malignancies (RR:1.28; CI:1.02-1.60; RR;1.45; CI:1.11-1.89 and RR: 1.45; CI:1.07-1.98, respectively). Sensitivity analysis in GnRH agonist-treated patients and in patients younger than 40 years old also revealed a significant benefit of GnRHa for the resumption of periods. CONCLUSIONS: Results of this meta-analysis suggest a potential protective effect with GnRH analogs administered during gonadotoxic chemotherapy for the preservation of ovarian function.
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ASRM Abstracts
P-189 Tuesday, October 31, 2017 REPRODUCTIVE KNOWLEDGE AND DECISION-MAKING AMONG THE OOCYTE CRYOPRESERVATION PAN. C. Stentz,b TIENT POPULATION. M. Shapiro,a L. W. Milman,c C. Gracia,d S. Senapati.e aObstetrics and Gynecology, BWH/MGH Integrated Residency Program in Ob/Gyn, Boston, MA; bReproductive Endocrinology & Infertility, University of Pennsylvania, Philadelphia, PA; cAbington Reproductive Medicine, Philadelphia, PA; dUniversity of Pennsylvania, Philadelphia, PA; eObstetrics & Gynecology, Reproductive Endocrinolog, University of Pennsylvania, Philadelphia, PA. OBJECTIVE: To compare the reproductive knowledge and desires of women presenting for oocyte cryopreservation consults to that of the general population of reproductive-age women in the US. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Using a previously validated questionnaire, women presenting for oocyte preservation consultation (Consult Group) (48 medically indicated, 36 elective) were compared to a national sample of 1000 reproductive-age women (National Group). Assessments were completed on demographic and medical history, reproductive health knowledge, and options towards and willingness to pay for fertility preservation. RESULTS: Women presenting for oocyte cryopreservation consults were older, had attained a higher level of education, employment, insurance, and income, and were less likely to be partnered than the National Group (p<0.05, all values). While both groups desired an average of 2 children, the Consult Group preferred a later age at first and last pregnancy, were less likely to consider maternal age in the decision of when to have a child, and were more likely to overestimate the age at which a woman has the greatest decline in fertility when compared to the National Group (p<0.05, all values). Interestingly, while women in the Consult Group were more likely to have ultimately frozen eggs (p<0.001), they also were more likely to overestimate the chance of pregnancy per frozen egg when compared to the National Group (p<0.001). At all theoretical chances of conception with frozen eggs (60% to 10%), women in the Consult group were willing to pay 10-times more for oocyte cryopreservation than the National Group (p<0.001). When asked about what percent chance of successful live birth one would be willing to accept after spending $10,000 to freeze eggs, women in the Consult group were willing to accept a lower chance of success than those in the National Group (50.7% vs. 73.1% respectively, p<0.001). CONCLUSIONS: Significant differences exist between women presenting for oocyte cryopreservation consultation and the general reproductive-age female population. Despite clinical counseling, significant knowledge gaps exist in the oocyte cryopreservation population, particularly regarding the potential success of oocyte cryopreservation. Improved and targeted education is needed to help women make more informed decisions regarding this evolving technology. Supported by: University of Pennsylvania FOCUS Medical Student Fellowship in Women’s Health, T32HD007440-20; 5K12HD001265. P-190 Tuesday, October 31, 2017 SINGLE-INCISION LAPAROSCOPIC SURGERY (SILS) FOR OVARIAN TISSUE CRYOPRESERVATION ENABLES HIGHER TISSUE VOLUME EXTRACTION AND EARLIER CHEMOTHRAPY INITIATION COMPARED TO STANDARD MULTIPORT LAPAROSCOPY. A. Revel,a N. Schachter-safrai,b H. H. Chill,c G. Karavani.d aReproductive Medicine and IVF Unit, Reproductive Medicine and IVF Unit, Zeriffin, Israel; bObstet and Gynecology, Hadassah Medical Center, Jerusalem, Israel; cReproductive Medicine and IVF Unit, Reproductive Medicine and IVF Unit, Jerusalem, Israel; dObstetrics and Gynecology, Hadassa- Hebrew University Medical Center, Jerusalem, Israel. OBJECTIVE: To compare tissue preservation and clinical outcomes of single-incision laparoscopic surgery (SILS) standard versus multi-port laparoscopy for ovarian tissue cryopreservation (OTC)in oncologic patients. DESIGN: Retrospective cohort study at tertiary academic medical center. MATERIALS AND METHODS: Two hundred thirty-one patients who underwent OTC from 1997 through 2017 in our tertiary medical center. Three-port laparoscopic surgery was performed in 165 (71.4%) patients and SILS was performed in 66 (28.6%) patients. Analysis included age at preservation, indication for OTC, chemotherapy prior to surgery, duration of the procedure, intra and post-operative complications, hospital stay, days from surgery to definite treatment (chemotherapy or radiation), number of oocytes and volume of tissue (assessed by number of ampules - each ampule contains 6-10 slivers for one grafting) preserved. Statistical evaluation including logistic regression was performed in order to compare the two surgical methods.
Vol. 108, No. 3, Supplement, September 2017
CHANGE IN MORPHOLOGICAL GRADE IMPROVE (n¼509) DOWNGRADE (n¼169) Implantation Clinical pregnancy Early pregnancy loss ICM
57.8%* (294/509) 54.2%* (276/509) 15.5% (79/509) IMPROVE (n¼109)
Implantation Clinical pregnancy Early pregnancy loss TROPHECTODERM
60.6%*+ (66/109) 56.9%*+ (62/109) 14.7% (16/109) IMPROVE (n¼56)
Implantation Clinical pregnancy Early pregnancy loss
64.3%* (36/56) 58.9%* (33/56) 19.6% (11/56)
49.7%*+ (84/169) 46.2%*+ (78/169) 18.9% (32/169) DOWNGRADE (n¼61)
COULD NOT ASSESS (n¼37)
43.2%o (16/37) 40.5%o (15/37) 21.6% (8/37) COULD NOT ASSESS (n¼49) o o^ 34.4%* (21/61) 61.0% (1102/1807) 40.8%+^ (20/49) 32.8%+o (20/61) 56.4%o^ (1019/1807) 36.7%*^ (18/49) 22.9% (14/61) 16.8% (303/1807) 24.5% (12/49) DOWNGRADE (n¼248) SAME (n¼1669) COULD NOT ASSESS (n¼49) 60.6%+ (1012/1669) 40.8%*+o (20/49) 56.0%o (139/248) 56.1%+ (937/1669) 36.7%*+o (18/49) 52.0%o (129/248) 16.1% (40/248) 16.8% (280/1669) 24.5% (12/49)
CONCLUSIONS: Dynamic changes in morphology may provide insight into an embryo’s ability to recover from the microenvironmental stress of vitrification-warming. A downgraded ICM conferred a negative prognosis, whereas a downgraded TE did not impact clinical outcome. Implantation failure and early pregnancy loss increased after transfer of warmed blastocysts whose ICM and TE could not be graded due to delayed reexpansion. These results suggest that rapid recovery and re-expansion after warming is associated with superior developmental competence and may serve as a clinical marker of embryo quality. P-186 Tuesday, October 31, 2017 LONG TERM CO-TRANSPLANTATION OF HUMAN OVARIAN TISSUE WITH AMH-PRODUCING ENDOTHELIAL CELLS INCREASE PRODUCTIVITY AND LONGEVITY OF THE GRAFT. L. Man, R. Bodine, L. Park, N. Zaninovic, G. L. Shatmann, Z. Rosenwaks, D. James. CRMI Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, NYC, NY. OBJECTIVE: A major obstacle to salvaging a robust pool of functional follicles from cryopreserved ovarian tissue following auto-transplantation is the global activation of the follicular pool that occurs during the ischemic window. AMH has been suggested to exert a repressive input on activation and/or growth of follicles during normal folliculogenesis. We used lentivirus to engineer exogenous endothelial cells (exECs) to constitutively express and secrete AMH, aiming to reduce premature follicular mobilization and growth upon co-transplantation in long-term grafts. DESIGN: Xenograft of human ovarian tissue into NSG mice with cotransplantation of ECs, and ECs ectopically expressing human AMH. MATERIALS AND METHODS: In order to consolidate the phenomenon of activation, despite co-transplantation with ECs, we co-transplanted multiple grafts from a single patient and harvested at 2 (n¼3), 3 (n¼4), and 14 (n¼2) weeks. Also, ECs were transduced with lentiviral vectors linked to a fluorescent reporter gene (mCherry) expressing AMH. Human ovarian tissue was co-transplanted with AMH-ECs into NSG oophorectomized mice (n¼2); as controls, we co-transplanted patient-matched ovarian tissue with ECs (n¼2). Engrafted tissue was harvested 14 weeks after transplantation. The ratio of follicles in each treatment was assessed in histologic sections using light and confocal microscopy. RESULTS: Control grafts harvested at 2, 3 and 14 weeks revealed a shift in the follicular pool away from quiescence with a decreased percentage of primordial follicles upon increased graft length. In contrast, grafts co-transplanted with AMH-ECs showed a significant retention of primordial follicles at 14 weeks. In these long-term grafts, we found a 4.6-fold increase in primordial follicles percentage with AMH-ECs; 18.390.75 vs. blankECs 3.991.61, P¼0.01. For primary follicles, we found a reverse ratio, an approximately 0.8-fold decrease compared to blank-ECs; 33.403.28 vs. 41.941.30 respectively, P¼0.05. CONCLUSIONS: Engineered exECs that constitutively express AMH induced a greater proportion of quiescent primordial follicles relative to control exECs, indicating suppression of premature mobilization that has been noted in the context of ovarian tissue transplantation. These findings present
FERTILITY & STERILITYÒ
SAME (n¼1176) 62.8%+o (738/1176) 57.7%+o (679/1176) 17.3% (203/1176) SAME (n¼1807)
P value *0.067 +0.001 o0.015 *0.068 o0.037 +0.0046 NS P value *0.001 +0.02 o<0.0001 ^0.004 *0.019 +0.003 o 0.0002 ^0.006 NS P value *0.016 +0.005 o0.05 *0.02 +0.007 o0.05 NS
a cell-based strategy that combines accelerated perfusion with a direct paracrine delivery of a bioactive payload to transplanted ovarian tissue. Improved tissue viability and enforced retention of a quiescent primordial follicle pool combine to increase productivity and longevity of ovarian tissue grafts. References: 1. Aubard, Y., Piver, P., Cogni, Y., Fermeaux, V., Poulin, N., and Driancourt, M.A. (1999). Orthotopic and heterotopic autografts of frozenthawed ovarian cortex in sheep. Hum Reprod 14, 2149-2154. 2. Baird, D.T., Webb, R., Campbell, B.K., Harkness, L.M., and Gosden, R.G. (1999). Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C. Endocrinology 140, 462-471. 3. Newton, H., Aubard, Y., Rutherford, A., Sharma, V., and Gosden, R. (1996). Low temperature storage and grafting of human ovarian tissue. Hum Reprod 11, 1487- 1491. 4. Van Eyck, A.S., Jordan, B.F., Gallez, B., Heilier, J.F., Van Langendonckt, A., and Donnez, J. (2009). Electron paramagnetic resonance as a tool to evaluate human ovarian tissue reoxygenation after xenografting. Fertil Steril 92, 374-381. 5. Dolmans, M.M., Martinez-Madrid, B., Gadisseux, E., Guiot, Y., Yuan, W.Y., Torre, A., Camboni, A., Van Langendonckt, A., and Donnez, J. (2007). Short-term transplantation of isolated human ovarian follicles and cortical tissue into nude mice. Reproduction 134, 253-262. 6. Amorim, C.A., David, A., Dolmans, M.M., Camboni, A., Donnez, J., and Van Langendonckt, A. (2011). Impact of freezing and thawing of human ovarian tissue on follicular growth after long-term xenotransplantation. J Assist Reprod Genet 28, 1157-1165. 7. Kawamura, K., Cheng, Y., Suzuki, N., Deguchi, M., Sato, Y., Takae, S., Ho, C.H., Kawamura, N., Tamura, M., Hashimoto, S., et al. (2013). Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A 110, 17474-17479. 8. Suzuki, N., Yoshioka, N., Takae, S., Sugishita, Y., Tamura, M., Hashimoto, S., Morimoto, Y., and Kawamura, K. (2015). Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod 30, 608-615. Supported by: Supported by: Internal (CRMI funding). P-187 Tuesday, October 31, 2017 LETROZOLE SUPPLEMENTATION DURING OVARIAN STIMULATION ALTERS OOCYTE MATURATION RATES IN BREAST CANCER CANDIDATES FOR FERTILITY PRESERVATION. M. Grynberga C. Sonigo.b aDepartment of Reproductive Medicine and Fertility Preservation, H^opital Jean Verdier, Bondy, France; bDepartment of Reproductive Medicine, Jean Verdier Hospital, Bondy, France. OBJECTIVE: Oocyte and/or embryo vitrification after controlled ovarian stimulation (COS) represents the most established and efficient method of female fertility preservation (FP) before cancer treatment. However, traditional COS regimens are associated with supraphysiologic serum estradiol and are therefore not recommended in estrogen-sensitive diseases such as breast
e179
cancer (BC). As a result, specific protocol using aromatase inhibitors (letrozole) were developed. The present investigation aimed to investigate whether COS with letrozole supplementation (COSTLES) modifies ovarian response and follicle responsiveness to exogenous FSH in BC patients? DESIGN: Prospective study. MATERIALS AND METHODS: This is the first investigation comparing COSTLES and standard ovarian stimulation in BC patients. We studied 133 BC patients, 25 to 40 years of age, candidates for FP using oocyte and/or embryo vitrification following COS. Of these, 68 patients underwent COSTLES while 65 had standard GnRH antagonist protocol. All women had 2 ovaries, no history of chemotherapy, BMI<30 Kg/m2 and a breast tumor that was surgically removed. Serum anti-M€ ullerian (AMH) levels and antral follicle count (AFC) were systematically assessed before exogenous FSH administration (d0). Follicle responsiveness to FSH was estimated by the Follicular Output Rate (FORT) calculated from the ratio between the pre-ovulatory follicle count (PFC, 16-20 mm) on the day of oocyte triggering (dOT) and the d0 AFC. RESULTS: Women in the COSTLES and control groups were comparable in terms of age 33.44.7 vs. 33.83.5 years, respectively), BMI (21.63.1 vs. 22.62.4 Kg/m2) and ovarian reserve tests (AMH: 2.21.8 vs. 2.72.3ng/mL; AFC: 18.510.5 vs. 17.910.7 follicles). After comparable starting doses and total amount of exogenous FSH (30461332 vs. 29961344IU, respectively), the FORT index did not differ significantly between groups (33.824.6 vs. 37.219.8%, respectively), leading to a similar number of oocyte recovered (12.38.3 vs. 12.58.7 oocytes, respectively). However, oocyte maturation rates were significantly lower in COSTLES compared to standard protocol (67.319.7 vs. 76.320.1%, p<0.02). As a result, the number of metaphase 2 oocyte vitrified was lower in patients having received letrozole supplementation (8.12.6 vs. 9.63.4 oocytes, p<0.05 respectively). CONCLUSIONS: Despite similar response to exogenous FSH, BC patients having undergone COSTLES showed reduced oocyte maturation rates in comparison with those having received standard stimulation regimen. At present, there is no evidence that standard COS promotes the proliferation of residual tumoral cells following breast surgery. If not, the confirmation of our results would lead reconsidering the real interest of COSTLES before adjuvant chemotherapy. P-188 Tuesday, October 31, 2017 GONADOTROPIN-RELEASING HORMONE ANALOGS FOR GONADAL PROTECTION DURING GONADOTOXIC CHEMOTHERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS. N. Sofiyeva,a,b T. Siepmann,b,c K. Barlinn,c B. Ata,d E. Seli.a aYale University, New Haven, CT; bCenter for Clinical Research and Management Education, Dresden International University, Dresden, Germany; cDepartment of Neurology, University Hospital Carl Gustav Carus, Technische Universit€at Dresden, Dresden, Germany; dObstetrics and Gynecology, Koc University School of Medicine, Istanbul, Turkey. OBJECTIVE: To investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents. DESIGN: A systematic review and meta-analysis of randomized and nonrandomized controlled trials. MATERIALS AND METHODS: Major databases, systematic snowballing, registered ongoing trials were used for data extraction. Studies published prior to March 2017 were assessed. Studies conducted in reproductive-aged women (<45 years) with a study group (co-administration of GnRHa) and control group (chemotherapy without GnRHa) were included in the analysis. There was no restriction for publication language. Studies were excluded if participants were given estrogen and/or progesterone, or pelvic radiotherapy. The outcome measure was the resumption of menstruation. Statistical analyses were performed with STATA 14.2. RESULTS: The database search yielded 25,151 citations and 80 manuscripts were assessed as full-text. Nineteen studies (12 RCTs and 7 Cohort studies) published between 1987 and 2015 were included in the quantitative analysis, revealing a significant protective effect of GnRHa (n¼1,106; RR:1.36; CI:1.151.61), although with high heterogeneity (I2¼82.2%). In subgroup analysis, a significant difference was detected in favor of GnRH co-treatment both in RCTs and cohort studies (RR:1.32; CI:1.06-1.64 and RR:1.42; CI:1.09-1.86, respectively). A significant benefit of GnRHa was approved in all subgroups by the underlying disease, i.e. breast cancer, autoimmune diseases, hematological malignancies (RR:1.28; CI:1.02-1.60; RR;1.45; CI:1.11-1.89 and RR: 1.45; CI:1.07-1.98, respectively). Sensitivity analysis in GnRH agonist-treated patients and in patients younger than 40 years old also revealed a significant benefit of GnRHa for the resumption of periods. CONCLUSIONS: Results of this meta-analysis suggest a potential protective effect with GnRH analogs administered during gonadotoxic chemotherapy for the preservation of ovarian function.
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ASRM Abstracts
P-189 Tuesday, October 31, 2017 REPRODUCTIVE KNOWLEDGE AND DECISION-MAKING AMONG THE OOCYTE CRYOPRESERVATION PAN. C. Stentz,b TIENT POPULATION. M. Shapiro,a L. W. Milman,c C. Gracia,d S. Senapati.e aObstetrics and Gynecology, BWH/MGH Integrated Residency Program in Ob/Gyn, Boston, MA; bReproductive Endocrinology & Infertility, University of Pennsylvania, Philadelphia, PA; cAbington Reproductive Medicine, Philadelphia, PA; dUniversity of Pennsylvania, Philadelphia, PA; eObstetrics & Gynecology, Reproductive Endocrinolog, University of Pennsylvania, Philadelphia, PA. OBJECTIVE: To compare the reproductive knowledge and desires of women presenting for oocyte cryopreservation consults to that of the general population of reproductive-age women in the US. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: Using a previously validated questionnaire, women presenting for oocyte preservation consultation (Consult Group) (48 medically indicated, 36 elective) were compared to a national sample of 1000 reproductive-age women (National Group). Assessments were completed on demographic and medical history, reproductive health knowledge, and options towards and willingness to pay for fertility preservation. RESULTS: Women presenting for oocyte cryopreservation consults were older, had attained a higher level of education, employment, insurance, and income, and were less likely to be partnered than the National Group (p<0.05, all values). While both groups desired an average of 2 children, the Consult Group preferred a later age at first and last pregnancy, were less likely to consider maternal age in the decision of when to have a child, and were more likely to overestimate the age at which a woman has the greatest decline in fertility when compared to the National Group (p<0.05, all values). Interestingly, while women in the Consult Group were more likely to have ultimately frozen eggs (p<0.001), they also were more likely to overestimate the chance of pregnancy per frozen egg when compared to the National Group (p<0.001). At all theoretical chances of conception with frozen eggs (60% to 10%), women in the Consult group were willing to pay 10-times more for oocyte cryopreservation than the National Group (p<0.001). When asked about what percent chance of successful live birth one would be willing to accept after spending $10,000 to freeze eggs, women in the Consult group were willing to accept a lower chance of success than those in the National Group (50.7% vs. 73.1% respectively, p<0.001). CONCLUSIONS: Significant differences exist between women presenting for oocyte cryopreservation consultation and the general reproductive-age female population. Despite clinical counseling, significant knowledge gaps exist in the oocyte cryopreservation population, particularly regarding the potential success of oocyte cryopreservation. Improved and targeted education is needed to help women make more informed decisions regarding this evolving technology. Supported by: University of Pennsylvania FOCUS Medical Student Fellowship in Women’s Health, T32HD007440-20; 5K12HD001265. P-190 Tuesday, October 31, 2017 SINGLE-INCISION LAPAROSCOPIC SURGERY (SILS) FOR OVARIAN TISSUE CRYOPRESERVATION ENABLES HIGHER TISSUE VOLUME EXTRACTION AND EARLIER CHEMOTHRAPY INITIATION COMPARED TO STANDARD MULTIPORT LAPAROSCOPY. A. Revel,a N. Schachter-safrai,b H. H. Chill,c G. Karavani.d aReproductive Medicine and IVF Unit, Reproductive Medicine and IVF Unit, Zeriffin, Israel; bObstet and Gynecology, Hadassah Medical Center, Jerusalem, Israel; cReproductive Medicine and IVF Unit, Reproductive Medicine and IVF Unit, Jerusalem, Israel; dObstetrics and Gynecology, Hadassa- Hebrew University Medical Center, Jerusalem, Israel. OBJECTIVE: To compare tissue preservation and clinical outcomes of single-incision laparoscopic surgery (SILS) standard versus multi-port laparoscopy for ovarian tissue cryopreservation (OTC)in oncologic patients. DESIGN: Retrospective cohort study at tertiary academic medical center. MATERIALS AND METHODS: Two hundred thirty-one patients who underwent OTC from 1997 through 2017 in our tertiary medical center. Three-port laparoscopic surgery was performed in 165 (71.4%) patients and SILS was performed in 66 (28.6%) patients. Analysis included age at preservation, indication for OTC, chemotherapy prior to surgery, duration of the procedure, intra and post-operative complications, hospital stay, days from surgery to definite treatment (chemotherapy or radiation), number of oocytes and volume of tissue (assessed by number of ampules - each ampule contains 6-10 slivers for one grafting) preserved. Statistical evaluation including logistic regression was performed in order to compare the two surgical methods.
Vol. 108, No. 3, Supplement, September 2017