Question 1- What is fertility preservation?
Fertility preservation essentially means preserving the ability of an individual woman or couple to conceive at a later date. These days, women are going for fertility preservation for a number of reasons. These include –
a) Women diagnosed with cancers and being planned for cancer treatment
b) Women undergoing treatment for Rheumatic diseases like Rheumatoid Arthritis and SLE and Myelodysplasia, which require them to take medications which can harm their fertility
c) Social indications – women not wanting to conceive at a young age for reasons such as career aspirations or if they are still looking for a suitable partner
This article discusses fertility preservation for women who are diagnosed with cancers and are going for cancer treatment. Fertility preservation carried out prior to the cancer treatment plays an important role in improving the quality of life of women surviving cancers. We counsel all women of reproductive age group, who are planned for cancer treatment and offer this option to all women who wish to preserve their fertility.
Question 2 – Why should a woman diagnosed with cancer worry about her fertility?
According to the National Cancer Registry of India, the number of newly diagnosed cases of cancer in India will cross the figure of 11 Lakh by year 2020, more than half of whom will likely be women. Of these, approximately two Lakh will be in adult patients within their reproductive years, i.e. up to age of 45 years.
Abdominal surgeries, especially the ones performed for treatment of cancers of reproductive organs – ovaries and uterus can cause permanent damage to the reproductive organs. Similarly, chemo and radiotherapy for cancers also affect the reproductive potential of women, as they have potential to cause genetic and structural damage to the reproductive organs. According to estimates, approximately 40-80% of women receiving cancer treatment are at risk of infertility resulting from cancer treatments in form of chemotherapy, radiation therapy and surgery.
Question 3 – How does cancer chemotherapy affect fertility of a woman?
Chemotherapeutic drugs kill cancer cells by interrupting critical cellular processes and stopping cellular growth and multiplication. But, these drugs can also cause DNA abnormalities and oxidative damage to the normal germ cells (cells which produce eggs) of a woman, leading to death and deformities of developing oocytes. The degree of damage to oocytes depends upon the specific drug that is used and its dose and also on age of the patient receiving this treatment. Older women with relatively lower ovarian reserves are more likely to be affected by the drugs, which can actually lead to premature ovarian failure (POF). The resulting damage to the ovaries can manifest in form of either temporary amenorrhea or premature menopause, both resulting in infertility.
Question 4 – How does radiation therapy affect fertility of a woman?
Radiation therapy can affect both ovary and uterus, thus impacting the fertility potential of the woman. Radiation induced damage to reproductive organs can cause infertility, miscarriage, preterm labor, intrauterine growth retardation and low birth weight. Radiations damage myometrium (inner lining of the uterus), and reduce its blood supply, which cause uterine fibrosis and hormone dependent endometrial insufficiency. The amount of damage caused to the ovaries by radiations depends upon age of the patient and amount of radiation exposure to the ovaries. Over 90% of patients undergoing total body irradiation or total abdominal irradiation eventually end up with ovarian failure.
Question 5 – What are various methods of preserving fertility among women?
There are multiple techniques, which can help women preserve their fertile potential for future and there are some other techniques, which are still emerging. The five main fertility preservation methods are explained below.
1. Embryo cryopreservation
Embryo cryopreservation means freezing embryos for implantation at a later (more suitable) occasion. This requires the patient to undergo IVF before starting the treatment for cancer. The embryos thus formed are then frozen. Embryo freezing is a proven and established technique and offers good results, which of course depend on the number and quality of embryos frozen.
Limitations of embryo cryopreservation:
a) Controlled ovarian stimulation in order to procure the eggs can take between 2-4 weeks’ time, depending on when the patient consults for fertility preservation. This means that the treatment for cancer has to be delayed by that many days, which may not always be in the best interest of the patient.
b) High Serum E2 levels resulting from hormonal stimulation of ovaries may have a negative effect on estrogen-sensitive tumors. We always seek an expert opinion from an oncologist before starting the stimulation.
c) IVF may not be possible in/ preferred by unmarried women, as it required sperms at the time of the procedure, and some women may not want to limit their reproductive autonomy in the future.
d) There are serious ethical and legal implications regarding disposal of the embryos, in case patient dies before she can use the embryos.
e) IVF cannot be used a fertility preservation technique for pre-pubertal girls undergoing treatment for cancers.
2. Mature oocyte cryopreservation
Oocyte cryopreservation (commonly referred to as Egg Freezing) is a preferred method of preserving fertility, especially among unmarried women as it allows the women to maintain their reproductive autonomy in future. However, egg freezing also required the patient to undergo controlled ovarian stimulation and, therefore, suffers from some of the same disadvantages as embryo freezing.
Just like embryo cryopreservation, egg cryopreservation can also not be used to preserve fertility potential among pre-pubertal girls. Also, since only a limited number of eggs/ embryos can be frozen is one cycle, the patient can take only as many attempts at pregnancy in future.
We recommend only one single attempt at stimulation and egg retrieval in order not to delay start of cancer treatment. We also take extreme care during stimulation so as to minimize the chance of ovarian hyper stimulation. The patients undergoing stimulation for fertility preservation are monitored very closely for ovarian response and dose of stimulation is titrated accordingly.
3. Ovarian tissue cryopreservation (OTC)
Ovarian tissue cryopreservation or tissue freezing is the process of harvesting ovarian cortical tissue (containing primordial follicles), dissecting the tissue into small pieces and freezing them for use later on. In most of the cases, this procedure can be performed laparoscopically (key hole surgery) and is done before starting any treatment for cancer. The frozen ovarian tissue can be re-transplanted into the patient on completion of cancer treatment, either into the pelvis (called orthotopic transplant) or in abdominal wall or forearm (called heterotopic transplant).
There is possibility of natural conception with orthotopic pelvic transplant of the ovarian tissue, but the patient definitely needs IVF treatment to conceive after heterotopic transplant of ovarian tissue. We always suggest orthotopic transplantation as a preferred method, as it is more biological and has better success rates.
Indications of Ovarian tissue cryopreservation-
a) Patient age less than 37 years
b) Good ovarian function – S FSH, AFC, AMH
c) Pre-pubertal girls where egg/ embryo freezing is ruled out
d) High risk for Permanent ovarian failure as a result of cancer treatment
Advantages of OTC over egg/ embryo freezing-
a) There is no need to delay cancer treatment in order to do OTC
b) There is no risk of ovarian hyper-stimulation and negative effect of progesterone on cancer
c) Partner or donor sperm is not required at the time of performing OTC, thus woman’s reproductive autonomy is maintained.
d) OTC helps preserve a larger number of follicles and technically allows for the resumption of ovarian function, which may last then many years.
However, OTC is still not a common fertility preserving method, especially for systemic cancers like leukemia, wherein cancer cells may be present in the frozen ovarian tissue. We consider OTC as a fertility preservation technique only in cases where egg/ embryo freezing is not indicated, namely when delaying start of cancer treatment not an option acceptable or controlled ovarian stimulation using hormones is contraindicated or IVF is not possible. OTC does not work for women over 40 years of age, as their ovarian reserve is relatively poor.
4. Fertility-sparing surgery – Ovarian transposition
Patients needing radiation treatment can benefit by fertility sparing surgeries. But, ovarian transposition is not an option for patients needing combined radiation- chemotherapy, which is a case in majority of patients. This procedure involves surgically moving the ovaries away from the field of radiation. For example-
a) Lateral fixation of ovaries in patients needing craniospinal irradiation
b) Moving ovaries out of the pelvis or into the anterior abdominal wall in patients who require radiation therapy to the pelvis
Disadvantages of ovarian transposition-
a) Risk of cyst formation in ovary and postoperative adhesions leading to chronic pelvic pain
b) Some patients may be harboring metastatic cancer in the ovaries, which may skip the radiation treatment
c) Transvaginal ovum pickup is not a viable option if the ovaries have been transposed and the patient may need laparoscopic egg pick up for IVF.
5. In vitro maturation
In vitro maturation (IVM) is another technique of fertility preservation for patients with cancers, but the success rate of IVM remains lower than egg/ embryo freezing. IVM involves aspiration of immature follicles (with/ out hormonal stimulation) for maturation outside of the body. The mature oocytes or embryos thus generated are then frozen for use at a later occasion.