Fertility preservation in female cancer patients

Chemotherapy and radiation or harmful to germ cells, causing damage to DNA and results in cell death.

Loss of germ cells in lead to decreased fertility and premature ovarian senescence.

Germ cells may be preserved prior to chemotherapy/radiation exposure allowing some women do have their own genetic children.

Treatment options depend on the tumor’s location and required therapy.

For cancers requiring pelvic radiation, standard options include shielding to reduce radiation damage to reproductive organs, or ovarian transposition.

For some gynecologic cancers surgical resection can preserve the reproductive organs, such as in low-grade and early-stage cancers with low malignant potential.

Radical trachelectomy may be considered for the treatment of early-stage invasive cervical cancer, for fertility sparing.

For patients exposed to systemic cytotoxic therapy the risk of infertility increases, especially in older women with fewer ovarian follicles: typical process for fertility preservation is cryopreservation of embryos or oocytes following controlled ovarian stimulation, which requires 2 to 6 weeks, depending upon the phase of the menstrual cycle at the time of initiation of therapy.

The extracted oocytes are fertilized in vitro and cryopreserved as embryos.

The banking of eggs and embryos are currently excepted fertility preservation options.

Unfertilized oocytes can also be frozen by vitrification techniques to improve locate survival and fertilization rates.

Methods for obtaining germ cells for fertility preservation include : ovarian tissue harvesting, in which a part or all of the ovary, with its germ cells, can be surgically removed and cryopreserved for autologous grafting.

In vitro maturation and cryopreservation of any immature oocyte can be retrieved from antral follicles of the ovary can be performed.

Ovarian stimulation and retrieval of mature oocytes, followed by thawing, fertilization and transfer.

Ovarian stimulation and retrieval of immature oversize, followed by cryopreservation for subsequently thawing , in vitro maturation, fertilization and transfer.

Ovarian stimulation with in vitro fertilization with partner/donor sperm and subsequent cryopreservation of resulting two pro-nuclear zygotes.

Standard IVF cycle takes approximately 2 weeks from initiation of ovarian stimulation until oocyte retrieval can be performed.

Ovarian tissue cryopreservation with later reimplantation/transplantation of tissue is a new technique for preserving the reproductive and hormone functions of patients who are prepubertal or not eligible to postpone their life-saving cancer therapy.
Indications for fertility preservation include premature ovarian insufficiency due to exposure to chemotherapy or radiation.
Ovarian damage related to chemotherapy varies by the type and dose of treatment and the radiation dose, the radiation field, and the fractionation plan.
The age of patients and ovarian reserve at the time they receive treatment are   prognostic  for the extent of fertility decline.
Cancer and anti-cancer treatments may affect post treatment ovarian function by a reduction in ovarian reserve; a disturbed hormonal balance; or by anatomical a functional changes to the ovaries, uterus, cervix, or vagina.
Reduce the ovarian function may resolve in infertility, and premature ovarian insufficiency.
Ovarian reserve can be estimated by measuring serum anti-Mullerian hormone levels and/or antral follicle count.
Alkylating agents can cause single and double strand DNA breaks with injury to both quiescent in dividing ovarian cells.
Ovarian tissues exposed to alkylating agents exhibit critical fibrosis and blood vessel damage compared with tissues not so exposed.
Higher cumulative doses of alkylating agents for childhood cancer results in acute ovarian insufficiency, premature menopause, poor reproductive outcomes such as small for gestational age offspring.
Presently, cryo-preservation of oocytes and embryos after controlled ovarian stimulation is the standard strategy for fertility preservation in adult women: several studies have reported that ovarian stimulation for fertility preservation in the setting of breast cancer is safe with regard to relapse free and overall survival.
In a Swedish study of  425 women with breast cancer who underwent fertility preservation at the time of breast cancer diagnosis was associated with significant higher rate of post diagnosis live births and assisted reproduction treatments, without any negative association with all-cause survival during fertility preservation.
Anti-Mullerian hormone concentrations are reduced substantially after initiation of chemotherapy and pre treatment levels and subsequent observations can predict the extent of chemotherapy induced ovarian damage.
Pelvic radiation treatments can lead to ovarian damage, reduction in uterine vascularity and uterine volume, myometrial fibrosis, endometrial damage, and other hormonally dependent gynecologic insufficiencies.
Pelvic radiation is associated with poor obstetrical outcomes with increased risk of abortions, preterm pregnancy, and low birth weight.
For the ovary less than 2Gy is sufficient to destroy more than 50% of human primordial follicles.
Ovarian failure is detected in 97% of women who are receive total abdominal radiation in childhood and 67% were receiving radiation in pre-puberty.
Bevacizumab is reported to have a risk of premature ovarian insufficiency in about 1/3 of its users.

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