Fertility Preservation in Cancer Patients and Beyond

FERTILITY PRESERVATION Shahrzad Zademodarres.MD Associate professor SBMU Winter 2015

introduction The increasing survival rates of cancer patients have encouraged many specialists to focus on the irreversible consequences of chemotherapy and radiotherapy. Similarly to cancer patients, there are some nononcological conditions currently treated with gonadotoxic agents, such as patients with autoimmune disorders or some chromosomal abnormalities that can lead to ovarian failure.

introduction There are also other situations where a woman may benefit from fertility preserva- tion procedures, such as a woman with severe or recurrent endometriosis or a woman who wants to postpone conception until her late reproductive years .

INTRODUCTION Risk factors for ovarian failure Age Ovarian reserve (FSH-AMH-AFC) Dose related

Effect of chemotherapy the drug dose dose-intensity method of administration (oral VS intravenous) disease age sex pretreatment fertility

effect of radiotherapy Direct damage to ovaries Damage to hypothalamic-pituitary axis

effect of radiotherapy Dose dependent: Total dose and fractionation schedule Age dependent: size of primordial follicle pool Radiation field Could also affect uterine function (M/C, IUGR, Premature deliveries)

Discuss the risk of infertility and fertility preservation options with patients with cancer anticipating treatment Medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons, as well as nurses, social workers, psychologists, and other nonphysician providers

Discuss fertility preservation with all patients of reproductive age (and with parents or guardians of children and adolescents) Refer patients who express an interest in fertility preservation (and patients who are ambivalent) to reproductive specialists

Address fertility preservation as early as possible, before treatment starts Document fertility preservation discussions in the medical record

Embryo cryopreservation Embryo cryopreservation is an established fertility preservation method, and it has routinely been used for storing surplus embryos after in vitro fertilization More flexible ovarian stimulation protocols for oocyte collection are now available

Embryo cryopreservation Timing of this procedure no longer depends on the menstrual cycle in most cases stimulation can be initiated with less delay compared with old protocols.

Embryo cryopreservation If the cancer patient presented in the late follicular phase: Ovarian stimulation without GnRH antagonist was started if the follicle cohort following the lead follicle was <12 mm and stayed <12 mm before a spontaneous LH surge

After the LH surge, GnRH antagonist was started when the secondary follicle cohort reached 12 mm to prevent premature secondary LH surge If the follicle cohort following the lead follicle reached 12mmbefore the spontaneous LH surge, pituitary suppression with GnRH antagonist was initiated and continued until triggering final oocyte maturation with hCG or GnRH agonist

If the patient presented in the luteal phase: ovarian stimulation was started in the absence of GnRH antagonist . Similarly to conventional COS, GnRH antagonist administration was initiated later in the cycle, when the follicle cohort reached 12 mm, to prevent premature secondary LH surge and was continued until the hCG or GnRH agonist trigger

Cryopreservation of unfertilized oocytes patients who do not have a male partner do not wish to use donor sperm have religious or ethical objections to embryo freezing.

Cryopreservation of unfertilized oocytes Oocyte cryopreservation should be performed in centers with the necessary expertise. As of October 2012, the American Society for Reproductive Medicine no longer deems this procedure experimental

Cryopreservation of unfertilized oocytes Steps of Oocyte Cryopreservation Program Concealing: Ovarian Hyperstimulation Egg Retrieval Oocyte freezing( Slow freezing/vitrification) Oocyte Thawing IVF/ICSI Embryo Transfer

Ovarian transposition Ovarian transposition (oophoropexy) can be offered when pelvic irradiation is performed as cancer treatment. because of radiation scatter, ovaries are not always protected, and patients should be aware that this technique is not always successful

Ovarian suppression there is insufficient evidence regarding the effectiveness of GnRHa and other means of ovarian suppression in fertility preservation

Ovarian tissue cryopreservation and transplantation Ovarian tissue cryopreservation for the purpose of future transplantation does not require ovarian stimulation or sexual maturity and hence may be the only method available in children.

Ovarian tissue cryopreservation and transplantation It is considered experimental and should be performed only in centers with the necessary expertise A theoretic concern with reimplanting ovarian tissue is the potential for reintroducing cancer cells depending on the type and stage of cancer, although so far there have been no reports of cancer recurrence.

Ovarian tissue cryopreservation and transplantation 11 Live birth till now in the world Ovarian reserve tests are needed before banking: FSH AMH AFC Most useful for hematopoeitic cell transplant To be offered to patients with a good long term prognosis

Conservative gynecologic surgery interventions to spare fertility have generally centered on doing less radical surgery with the intent of sparing the reproductive organs as much as possible. Ovarian cystectomy can be performed for early-stage ovarian cancer

estrogen-sensitive breast and gynecologic malignancies Ovarian stimulation protocols using the aromatase inhibitor letrozole have been developed and may ameliorate Studies do not indicate increased cancer recurrence risk as a result of subsequent pregnancy

Fertility preservation in children Suggest established methods of fertility preservation ( semen or oocyte cryopreservation) for postpubertal minor children, with patient assent and parent or guardian consent. For prepubertal minor children, the only fertility preservation options are ovarian and testicular cryopreservation, which are investigational

preservation of fertility in males Sperm cryopreservation is effective Hormonal therapy in men is not successful in preserving fertility. It is not recommended. testicular tissue cryopreservation and reimplantation or grafting of human testicular tissue, should be performed only as part of clinical trials or approved experimental protocols

preservation of fertility in males It is strongly recommended that sperm be collected before initiation of treatment because the quality of the sample and sperm DNA integrity may be compromised after a single treatment session