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Kristen Cain, MD, FACOG Reproductive Medicine Institute Sanford Health, Fargo, ND

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Kristen Cain, MD, FACOG Reproductive Medicine Institute Sanford Health, Fargo, ND Kristen Cain, MD, FACOG Reproductive Medicine Institute Sanford Health, Fargo, ND s Nothing to Disclose s Reproductive age patients value their fertility Survival of childhood and adult cancers is increasing Treatment and preservation options continue to evolve Failure to discuss fertility issues with young cancer patients can have lasting negative consequences Duffy C et al, Cancer J 2009, 15;27-33. Simon B et al CA Cancer J Clin 2005 55;211-228 Annually more than 130,000 cancer patients are diagnosed in their reproductive years (up to 45) 1 More than 11,000 breast cancer patients are diagnosed under the age of 40 each year 2 21% of gynecologic cancer patients are diagnosed under the age of 45 3 12,000 children (0-19) are diagnosed with cancer each year 4 5-7% invasive breast cancer cases occur in women under the age of 40 (www.seer.cancer.gov.2008 ) 1 American Cancer Society & U.S. Census Bureau 2 Young Survival Coalition 3 Liou WS, Yap S, et al., Fertility and Sterility, 2005. 4 Goodwin T, Ooosterhuis BE, et al., Pediatric Blood Cancer,s 2007. Increasing Cancer Survival Rates Increased Emphasis on Quality of Life + Many Successful Fertility Preservation & Post-treatment Parenthood Options = Patients Need Information About Fertility Risks & Options s Cancer Survivorship Rates are High 77% percent of patients under 45 survive at least five years 1 US Trend: Delayed Childbearing Average age for first child is 25.2 – an all time high 2 More patients have not had children when diagnosed Nearly ¼ of first-time live births occur to women over the age of 30 1 SEER Cancer Statistics Review, 1997-2004. 2 CDC, 2004. s US Trends in 5 Year Relative Survival 100 90 80 Breast (female) Colon 70 Kidney 60 Leukemia Lung/bronchus 50 NHL 40 Ovary 30 Pancreas Prostate 20 Uterine cervix 10 5 Year Relative Survival Rates (%) 0 1975-1977 1984-1986 1996-2004 Year of diagnosis American Cancer Society. Cancer Facts and Figures 2009. www.cancer.gov. s 7 US: Cancer Sites as Percentage of New Cancer Cases in 2009 Females Males Other Other Breast Prostate Lung/bronchus Lung/bronchus Colon/rectum Colon/rectum Uterus Bladder NHL NHL Thyroid Kidney Kidney Leukemia Ovary Oral cavity NHL = non-Hodgkin’s lymphoma. American Cancer Society. Cancer Facts and Figures 2009. www.cancer.org . s 4 Prostate cancer being diagnosed in younger men Radical prostatectomy=universal infertility Delayed fatherhood Childless Recent study showed 20% of prostate cancer patients who were asked about sperm freezing were interested (F&S Vol 100 No 2 August 2013) s As part of informed consent prior to therapy, oncologists should address the possibility of infertility with patients as early in treatment planning as possible 1 1 Lee SJ, Schover LR, et al., Journal of Clinical Oncology, 2006.s 2004 – President’s Cancer Panel 1 “Report on Survivorship” recognized infertility as a top concern and issued recommendations 2004 – ASRM Fertility-Preservation Special Interest Group formed 2005 – NICHD Created specialized fertility preservation research section 2006 – ASCO 2 Issued the 1 st Fertility Preservation Guideline 1 President’s Cancer Panel, 2003-2004 Annual Report, May 2004. 2 Lee SJ, Schover LR, et al., Journal of Clinical Oncology, 2006.s s Females: 90% total gonadal failure after TBI Dose dependent Increased SAB rate (38% vs 12%) Increase Preterm labor rate (62% vs 9%) Males 80% gonadal failure after TBI Treatment field and dose dependent Critchley H Med Pediatr Oncol 1999 33;9-14. Critchley H Hum Fertil 2002 5;61-66. Cranial: Interrupts hypothalamic pituitary gonadal axis Pelvic: Reduces sperm production, azoospermia if >1/2Gy Disrupts Leydig cell function, testosterone production Ovarian failure Reduced volume and elasticity of uterus s Reduced testosterone Leydig cell dysfunction Germ cell failure Decreased, damaged, or absent sperm Damage to duct system to transport sperm Ejaculatory dysfunction Damage to pelvic nerves Sexual and ejaculatory dysfunction s Fertile Hope, Fast Facts for Oncology Professionals, 2007 s • History – Delayed/arrested puberty – Menstrual/pregnancy history – Sexual dysfunction: vaginal dryness, libido, etc… • Physical exam – Height, weight, Tanner stage – Estrogen effect • Laboratory – Elevated FSH – Low estradiol s s Sperm is collected by masturbation Can be obtained after spermarche age 13-14 Sperm can be stored safely for many years Only limit to number of collections is money and time Once radiation and chemotherapy has begun, collection must be stopped Safe, outpatient, painless Advise semen analysis 6-12 months after completion of treatment to reassess s Successful in mice No attempt in humans yet Testicular biopsy prior to cancer Rx Biopsy tissue immediately frozen When ready, tissue thawed and stem cells are propagated in vitro New spermatogonia are autotransplanted after cancer treatment is complete s Need to avoid reintroduction of tumor cells Non-toxic media conditions for propagation Genetic stability of sperm: O2, temp Getting enough to populate an adult sized testis Epigenetics Colonization of the tubules Struijk R et al, Biomed Res Int 2013 2013;903142 Intrauterine insemination Cheap Easy Female partner needs monitoring, ?meds Need a lot of sperm IVF/ICSI Expensive Female partner need IVF, meds, monitoring ICSI injects sperm directly into the oocyte Need a little sperm, unused sperm can be refrozen s Sperm is screened and stored according to FDA protocols Donors undergo psychological, STD, genetic and general health screening Sperm is quarantined for 6 months and donor is rescreened Female partner can time inseminations with at home LH kit Relatively inexpensive Unlimited supply s s Embryo, oocyte, and ovarian tissue freezing Ovarian transposition GnRH-analogs In vitro maturation Autologous ovarian transplantation In Vitro Maturation Oocyte donation Gestational Surrogacy Adoption s Mature eggs removed, fertilized with sperm, frozen and stored Embryos can be stored for many years 1 Females, after puberty 2-6 weeks, depending on menstrual cycle Pregnancy rates 28% per cycle (similar to fresh IVF success rates) 2 Thousands of babies born worldwide 2 1 Summers-Chase D, Check JH, et al., Fertility and Sterility , 2006. 2 SART & ASRM, Fertility and Sterility , 2007. s s 3 patients with breast cancer Letrozole/FSH started on cD11, 14, and 17 9-17 oocytes retrieved 7-10 embryos available for cryopreservation Allows immediate start for IVF May allow for multiple procedures prior to chemotherapy and radiation Sonmezer, M et al, F&S, Feb 2011, epub Tamoxifen and aromatase inhibitors (letrozole) can be used for ovulation induction Low dose FSH is added to create a satisfactory # of follicles Good stimulations with low peak E2s GnRH analog trigger, rather than HCG: also reduces risk of OHSS, VTE Disappointing response may be seen in young patients with breast cancer (BRCA pos associated with poorer egg quality) Reddy,J et al, Fertility Sterility 2012 98;1363-1369 Mature eggs removed, frozen and stored Technically challenging: Oocyte is largest cell in body, mostly water Prone to intracellular ice formation, spindle disruption Two methods – slow freezing or vitrification Female, after puberty 2-6 weeks, depending on menstrual cycle Clinical pregnancies/per transfer 20.6% 1 1500+ babies born worldwide (2007 data) 1 Tur-Kaspa, ASRM Abstract, 2007 . See also Nature 25 Octobers 2007 Vol. 449 No. 7165, pp947-1088 . Experimental Immature eggs collected without ovarian stimulation, matured for 24-48 hours in vitro, and fertilized by ICSI Females, before and after puberty Embryo implantation rates are low ~11% 1 vs. IVF 38% clinical pregnancy rate per cycle in women ≤ 35 2 50% in recipients of IVM egg donation 2 Over 1,000 babies have been born worldwide using IVM 3 May 12, 2007: Birth of the first baby conceived from an in vitro-matured, frozen-thawed egg 1 ESHRE International Symposium on In Vitro Maturation of Oocytes, 2007. 2 Rao GD, Tan SL, Semin Reprod Med , 2005. 3 ESHRE International Symposium on In Vitro Maturation ofs Oocytes, 2007. Experimental Ovary removed laparoscopically, divided into small strips, frozen and stored Females, before and after puberty Only option for prepubescent girls Outpatient surgical procedure 13 live births reported to date (F&S April 2011) Ovarian tissue transplant in over 30 women, no cases of micrometastases. 1 Donnez J, Martinez-Madrid B, et al., Hum Reprod Update s, 2006. s Administered during chemo to induce pre- pubertal state; may limit damage to immature follicles, reducing chance of infertility 1 Females, after puberty Monthly injection Experimental, latest studies 2 show no effect 1 Blumenfeld Z, J Soc Gynecol Investig , 2001. 2Fox KR, Ball JE, et al., 39 th Annual ASCO Meeting, 2003. 2 s Women can choose known or anonymous donor Women who are infertile or in menopause can still carry a pregnancy using donor eggs or embryos Donor eggs can be fertilized with partner’s sperm to create embryos that are genetically related partner Success rates higher than standard IVF 60-80% pregnancy rates SART 2010 One or more embryos transferred to the uterus of another woman May allow patient to have biological offspring even if unable to carry a pregnancy Can use own embryos or donor eggs or embryos Pregnancy rates range from 18 to 30 %, 1,2 depending on the quality of the eggs or embryos used Laws vary by state 1 Brinsden PR, Hum Reprod Update , 2003. 2 SART & ASRM, 2007. s Excellent
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