Dr Kamini A Rao

 Over individuals under 45 years are diagnosed of cancer annually in US.  Improved treatment and survival  Fertility preservation is a quality-of-life issue.

 Factors contributing to ovarian failure: Age at time of treatment Drug type Cumulative dose  Cyclophosphamide: Most gonado-toxic  Cumulative dose strongly influences POF rate  Pelvic or total body irradiation also has high risk of POF

 No ideal marker  ↑ FSH  ↓ AMH  ↓ ovarian volume  AFC similar to controls  Transient suppression of inhibin B in pre-pubertal girls.

1. Young cancer patients 2. Childhood pelvic tumours: Ewing’s sarcoma, osteosarcoma, retroperitoneal sarcoma, anorectal cancer 3. Wilm’s tumour, neuroblastoma, rhabdomyosarcoma 4. Autoimmune disorders – SLE, Behcet’s disease, steroid resistant glomerulonephritis 5. Chemotherapy for bone marrow transplantation and stem cell transplantation

 15% of all breast cancer cases are estimated to occur in women <40yrs age Jemal A et al. Cancer statistics, CA Cancer J Clin 2003  Majority patients – multiagent cyclophosphamide based therapy

 Embryo cryopreservation  Oocyte or ovarian tissue freezing  Surgery → COH (2–3 weeks) → chemo/radiotherapy  Modified COH → High estradiol levels can be harmful Drugs like letrozole, tamoxifen should be used. Careful of OHSS (causes delay in treatment), risk of thromboembolism in carcinoma.

 Common in reproductive age  Fertility preservation Ovarian transposition during radiotherapy Embryo/ oocyte cryopreservation Ovarian tissue freezing  Special care during egg collection due to friability of tissue  Trans-myometrial embryo transfer may be necessary

 Unilateral salpingo-oophorectomy - ↓ ovarian volume - ↓ oocyte count  Previous adjuvant chemotherapy - ↑ gonadotrophins dose (i.e. 450 IU daily) to induce an adequate ovarian response.

 2-14% of premenopausal women (Crissman et al., 1981; Gitsch et al., 1995; Kempson and Pokorny,1968).  Preservation of the uterus Hormonal therapy - oral progestational agents, such as medroxyprogesterone acetate or megestrol Levonorgestrel-containing intrauterine device

 Tumour burden high at the outset of diagnosis  Cancer therapy should begin almost immediately.  If no window of opportunity exists, ovarian tissue or oocyte harvest with IVM can be considered

 Only practical option in single women  Oocyte subcellular organelles more complex more sensitive to cryoinjury Low survival after thawing

 Most efficient technique and recommended procedure  Embryo have better survival after thawing compared to oocytes  Counsel regarding success rates  Reasonable opportunity for success Partner availability Time available before chemotherapy for stimulation

 Problematic for patients with estrogen- sensitive tumors such as breast cancer.  Natural-cycle (un-stimulated) IVF-single oocyte, high cancellation rates.  Majority of malignancies do not permit delay in treatment.  Availability of partner necessary for IVF

Counseling  All females should have the opportunity of discussing the preservation of their fertility with an appropriately trained person prior to gonadotoxic therapy or removal of ovarian tissue.  Parents of children - discuss children’s gonadal tissue conservation  Consent for gonadal tissue conservation(consent for options after DEATH)  Rationale and need for relevant research should be explained  Consent to use a part of the tissue for research  Psychosocial counseling  Long term record keeping  Financial implications (not insurance covered)

 Procedure should not harm patient by delaying treatment  All attempts made to ensure no malignant cells are re-introduced

 Ejaculated sperm cryopreservation  Ejaculatory dysfunction –use PDE 5 inhibitors, vibrator, electro-ejaculation.  Counsel regarding side-effects of each of these methods.  Cryopreservation of surgically extracted sperms(PESA, MESA,TESA,TESE,micro TESE)

 Unexplained infertility  Recurrent pregnancy loss(Defective placentation, placental insufficiency)  Implantation failure  POF(as result of disease or as a result of cytotoxic drugs)

 RELATION TO INFERTILITY????  Amenorrhea accompanying severe flares.  Renal insufficiency-related hypofertility.  Ovarian failure secondary to cyclophosphamide (CTX) therapy.  Lupus flare associated with ovarian stimulation.  Thrombosis associated with OHSS.

 Badly controlled arterial hypertension  Pulmonary hypertension  Advanced renal disease  Severe valvulopathy  Heart disease  Major previous thrombotic events.

 Related to adverse pregnancy outcomes-  Increased risk of unexplained sub- fertility  Miscarriage  Recurrent miscarriage  Preterm birth  Maternal post-partum thyroiditis Emmy van den Boogaard,HR update 2011.

 Systematic screening of Thyroid autoimmunity and hypothyroidism during early pregnancy  Monitoring of thyroid function with/without L-thyroxine treatment  Follow-up during post-partum period

 Rheumatologic diseases often strike both men and women during childbearing years, and the diseases themselves as well as the long-term therapies used to treat them can have a negative impact on reproductive health.  The list of rheumatic drugs that are known to affect reproductive health includes, but may not be limited to, cyclophosphamide, chlorambucil, nonsteroidal anti-inflammatory drugs (NSAIDs), sulfasalazine, methotrexate, and leflunomide.  These drug may cause an arrest in follicular maturation, stromal fibrosis, and a decreased number of ova in the ovary, leading to delayed onset of menstruation and amenorrhea.” In adolescent and adult male patients, chlorambucil, either alone or in combination with prednisone or azathioprine, has been linked to temporary azoospermia,

 20% of POF have autoimmune disorders.  May be a result of destruction of primordial follicles or steroid producing cells as a result of autoimmunity or after cytotoxic chemotherapy.

 Embryo cryopreservation - currently most accepted option  Oocyte cryopreservation – upcoming valuable option  Ovarian tissue cryopreservation - currently experimental but promising in future  Despite the emotional vulnerability of cancer patients at the time of diagnosis - ethical obligation to advise them regarding the available options for fertility preservation