Download Fertility preservation in patients on cytotoxic therapy

Dr Kamini A Rao
 Over
100 000 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
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No ideal marker
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↑ FSH
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↓ AMH
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↓ ovarian volume
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AFC similar to controls
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Transient suppression of
inhibin B in pre-pubertal
girls.
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Young cancer patients
Childhood pelvic tumours: Ewing’s sarcoma,
osteosarcoma, retroperitoneal sarcoma, anorectal
cancer
Wilm’s tumour, neuroblastoma, rhabdomyosarcoma
Autoimmune disorders – SLE, Behcet’s disease, steroid
resistant glomerulonephritis
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, 2003. CA Cancer J Clin 2003
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Majority patients – multiagent
cyclophosphamide based therapy
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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.
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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
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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
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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
 POF(as
failure
result of disease or as a result of
cytotoxic drugs)
 RELATION
TO INFERTILITY????
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Amenorrhea accompanying severe flares.
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Renal insufficiency-related hypofertility.
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Ovarian failure secondary to cyclophosphamide (CTX)
therapy.
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Lupus flare associated with ovarian stimulation.
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Thrombosis associated with OHSS.
 Badly
controlled arterial hypertension
 Pulmonary
 Advanced
 Severe
hypertension
renal disease
valvulopathy
 Heart
disease
 Major
previous thrombotic events.
 Related
to adverse pregnancy outcomes Increased risk of unexplained subfertility
 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.
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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%
 May
of POF have autoimmune disorders.
be a result of destruction of
primordial follicles or steroid producing
cells as a result of autoimmunity or after
cytotoxic chemotherapy.
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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