Fertility Preservation in WomenDr Chinmayie R
Fertility preservation (FP) is a fundamental issue for individuals of reproductive age, both male and female, or prepubescent boys and girls whose future fertility may be compromised by conditions like cancers, genetic disorders associated with premature ovarian insufficiency(POI) like turners, Klinefelter and some non-malignant condition requiring chemotherapy for treatment like benign ovarian tumors, endometriosis, autoimmune disease, hematopoietic or bone marrow transplantation. Delayed marriage, especially in females, as the ovarian reserve decreases after 32yrs and rapidly after 37yrs. As infertility specialists, we are responsible for making the needy and oncologists aware of fertility preservation.
Cancer: Approximately 10% of the cancers occur in women less than 45yr. Advances in cancer therapy have caused a tremendous increase in the survival rates but at the cost of ovarian function.
1. Chemotherapeutic agents act on continuously dividing cells. These agents can damage DNA leading to cell death injured fertility outcomes depending on the ovarian reserve. Protector used for pretreatment alkylatingents is the most toxic.
• Ionising radiation has adverse effects on gonadal function at all ages. Effective Sterilization Dose decreases with age. Pelvic, Whole abdomen, and craniospinal radiation are the most harmful.
Methods of fertility preservation for women:
❖ Fertility sparing surgeries
❖ Protective adjuvant therapy
❖ Embryo cryopreservation
❖ Oocyte cryopreservation
❖ Ovarian tissue cryopreservation
❖ In vitro activation.
Fertility sparing surgeries:
❖ Ovarian Transposition
❖ Radical Trachelectomy
❖ Cone Biopsy
❖ Unilateral oophorectomy.
• Repositioning of the ovary outside the radiation field
• Laparoscopy is preferred• Effective way of fertility preservation in cervical carcinoma
• Right side is preferred than left
• Upto 90% success with brachytherapy for Cervix.
Protective Adjuvant therapy: GnRH agonists
❖ The hypogonadotropic milieu decreases the number of primordial follicles entering the differentiation stage, which is more vulnerable to chemotherapy;
❖ The hypoestrogenic state decreases ovarian perfusion and delivery of chemotherapy to the ovaries;
❖ A direct effect of the GnRH agonist on the ovary occurs independently of the gonadotropin level;
❖ GnRH agonists may upregulate an intragonadal antiapoptotic molecule such as sphingosine-1- phosphate;
❖ The GnRH agonist may protect ovarian germline stem cells.
Embryo and oocyte cryopreservation:
❖ Both are first-line fertility preservation methods
❖ Embryo cryopreservation is the first line of fertility preservation ever recommended
❖ Success rates are better with embryo cryopreservation compared to oocyte
❖ Oocyte preservation is more preferred compared to embryo preservation -Vitrification procedure has yielded similar results compared to that of fresh oocytes
❖ It avoids ethical and social issues associated with embryo preservation.
Stimulation protocols should be individualized depending on the type of cancer. Tamoxifen or aromatase inhibitors ( AI )are best for breast cancer, and for endometrial ca, AI is better.
❖ Only feasible option available for pre-pubertal girls and in those whose chemotherapy cannot be delayed
❖ Many have set an upper age limit of 35yr; it is followed by re-implantation of ovarian tissue after thawing of cryopreserved ovarian tissue, either by orthotropic transplantation( positioning back into the pelvis )or by heterotopic transplantation(elsewhere).
In vitro activation:Principle: Primordial follicles are dormant in ovaries. They get recruited by complex intracellular pathways. However, in POF, as the number of strands is deficient, they no longer get recruited by standard mechanism. Creating an environment in vitro which could activate the follicles is the basic principle of IVA. Stimulation of follicle growth by disruption of the Hippo signaling pathway. Hippo signaling leads to several negative factors, eventually deactivating the transcriptional factors.