Fertility Preservation Flashcards
What is the need for fertility preservation? (5)
Cancer, radiotherapy & chemotherapy can cause premature gonadal failure.
Associated somatic disorders such as fever, malnutrition, anxiety or depression may affect fertility.
20% of patients with premature ovarian failure have an autoimmune associated disease such as diabetes, thyroid dysfunction, Addison syndrome, Crohn’s disease etc.
Surgery, endometriosis, infection, family history of premature ovarian failure & idiopathic causes.
Women delaying child bearing due to social factors.
Cancer and fertility explained (4)
Half of people diagnosed with cancer now survive their disease for at least five years - cancer survival rates in the UK have doubled in the last 40 years.
Almost three-quarters of children are now cured of their disease, compared with around a quarter in the late 1960s.
Cancer therapy can result in infertility or premature gonadal failure leading to a significant quality of life issue for young survivors.
Approximately 75% of patients under 35 who are childless at the time of cancer diagnosis desire children in the future.
Surgery causing infertility - Males (4)
Unilateral orchidectomy reduces sperm concentration. Reduced spermatogenesis is reversible within the first year after surgery.
Retroperitoneal lymph node dissection can cause serious disruption of ejaculation (testicular or renal cell carcinoma).
Radical prostatectomy may lead to erectile dysfunction, retrograde ejaculation and poor semen quality.
Rectal cancer surgery may lead to erectile dysfunction.
Surgery causing infertility - Females (4)
Hysterectomy or oophorectomy may be performed.
In some women with early stage ovarian or cervical cancer it is appropriate to attempt to retain one ovary, both for future fertility and hormone production.
Patients with small cervical cancers may undergo trachelectomy, which removes the cervix but leaves the uterus in-situ.
Sometimes surgery can cause scarring in the uterine tubes which may obstruct them.
Radiotherapy causing infertility - Males (6)
Irradiation in the G2 phase of the cycle induces chromatid aberrations. Analyse dose/response of peripheral blood cells, enabling restriction of dose.
0.5 Gy: Transient suppression with subsequent recovery of spermatogenesis.
2–3 Gy: Period of azoospermia after which full recovery is expected within three years.
4–6 Gy: Recovery is not universal and may take up to five years.
6 Gy: High risk of permanent sterility.
Total body irradiation (TBI) with high-dose chemotherapy will sterilise men.
Radiotherapy causing infertility - Females (4)
Ovarian damage depends on patients age, dose & field of irradiation. Radiation to the pelvis can have a direct negative impact on ovarian function and the uterus by altering vascularisation.
Doses of 4-6 Gy can produce a loss of 50% of the follicle population.
Total body irradiation (typically 10-12 Gy) causes infertility, recovery of ovarian function occurs in 10- 15% of cases.
Non-pelvic radiation, especially head and neck may disrupt the hypothalamic-pituitary axis.
Chemotherapy causing infertility -Males (3)
Most chemotherapeutic agents are gonadotoxic. Alkylating agents pose the greatest risk to spermatogenesis.
DNA of spermatozoa can also be damaged by low doses of chemotherapeutic agents – DNA integrity may be recovered after treatment.
Not all chemotherapy regimens affect male fertility, preservation is only offered where a high risk of azoospermia or DNA damage is expected.
Chemotherapy causing infertility - Females (4)
Several mechanisms including follicular depletion, vascular damage, cortical fibrosis.
Alkylating agents such as cyclophosphamide are most gonadotoxic since they are not cell cycle specific and also affect other cells in the ovary. All patients exposed to chemotherapy might have a diminished ovarian reserve.
Younger patients 20% - 90% affected . Probability of early menopause is at least 25% at age 30 years. Infertility at 35 years >40%.
Women over 40 years have a 90% chance of amenorrhoea subsequent to multi-agent chemotherapy.
= instigates menopause
Patient psychological concerns & reactions (5)
Digesting the ‘double blow’. Bewildered and overwhelmed.
Feelings of being ‘out of control’ and struggling to regain a sense of personal stability.
Sense of being robbed of one’s manhood or womanhood.
Grief over the possible loss of the opportunity to fulfill one’s dreams.
Anger toward the medical community for failing to provide adequate information regarding fertility risks.
Fertility preservation options (7)
Pre-pubescent / adult males :Testicular tissue/cryopreservation - 1 day = Surgical removal of testicular tissue and maturation in- vitro/autotransplantation
image
Why would you partake in oocyte cryopreservation? (4)
Controlled ovarian stimulation using gonadotrophins for 8-12 days followed by oocyte retrieval.
Difficulties with slow freezing – ice crystal formation, low survival and poor embryo quality. Now becoming routine practice in IVF centres with the
development of oocyte vitrification.
Suitable strategy for patients who can postpone oncologic treatment and where COS is not contraindicated (x breast cancer- inc. oestrogen or can’t wait 1 month).
Valid option for post pubertal women without a male partner or those who do not want donor sperm or object to embryo cryopreservation.
Safely carrying out oocyte cryopreservation? (3)
The entire process takes a minimum of 2-3 weeks depending upon the patients menstrual cycle.
Exposure to high levels of estradiol is contraindicated. There is controversy on this issue with some authors arguing that a short- term increase is not harmful.
Ovarian stimulation protocols including aromatase inhibitors have been described in order to avoid excessive high estradiol levels. (women w/oestrogen receptor tumours)
Embryo cryopreservation (4)
Most standardised procedure
High embryo survival and cumulative pregnancy rates of 60%
Requirement for male partner or sperm donor.
Ethical implications of increasing numbers of embryos stored in IVF clinics make oocyte vitrification a preferred option in many cases. (custody battles over embryos)
In-vitro maturation of oocytes (4) - experimental
Retrieval of immature oocytes followed by in-vitro maturation.
One of the strategies in cases where ovarian stimulation is not possible.
Oocyte retrieval usually performed prior to ovulation, but immature oocytes
can be recovered during both follicular and luteal phases.
Vitrification of IVM oocytes has resulted in live birth rates <20%. Survival and
fertilisation rates lower than for oocytes matured in-vivo.
In-vitro follicle culture (2)
Proposed as an alternative to IVM, the aim being to develop an in-vitro system that allows growth of primordial follicles to antral stages in order to obtain mature oocytes.
Given the complexity of folliculogenesis, much research into culture conditions is still necessary in order to achieve results for clinical practice.
