Fertility Preservation

Fertility preservation refers to interventions that preserve fertility potential when the survival of either eggs or sperm is threatened.

What might threaten my fertility potential?

A variety of conditions are known to pose a threat to eggs and sperm.

Cancer treatment:
One of the most significant threats to fertility is cancer treatment. The drugs used during cancer treatment (known as chemotherapy) work by blocking the survival of cancer cells. Unfortunately, eggs and sperm are also very sensitive to many of these agents and may also be damaged during chemotherapy. Certain cancer agents such as the alkylating agents (e.g. cyclophosphamide) are especially toxic to sperm and eggs. The threat to ovarian function is greatest when function is already low, for instance, for women in their forties.

Ageing:
Natural ageing is a major threat to a woman’s fertility. This is because women are born with a fixed quota of eggs, which age as a woman gets older. Egg numbers also dwindle with age until they eventually run out at the time of the menopause. Eggs begin showing signs of deterioration in quality when women are in their thirties, and therefore at a relatively young age. Quality is the key property of the egg that is important for pregnancy success, so this deterioration has a significant impact on pregnancy chances, becoming especially marked by the late thirties. Ageing is less detrimental to men because they retain sperm-making cells in the testes (called germline stem cells) that can generate new sperm throughout life. Indeed, men make millions of sperm per day in contrast to women who are born with a relatively small number of around 1-2 million eggs.

Endometriosis:
In women with endometriosis who have endometriotic cysts (also known as endometriomas or “chocolate cysts”), these cysts can become quite large. As cysts enlarge, they erode normal ovarian tissue including their contained eggs. Surgery on endometriotic cysts can also be very dangerous to the egg reserve since removing endometriomas will also remove some of the normal surrounding ovarian tissue. Due to damaging effects that surgery can have on the ovarian reserve, it is intensely debated whether endometriomas should be removed or not prior to undergoing IVF, with many experts tending towards a more conservative approach of not undertaking surgery.

Genetic conditions:
In rare instances, females may be born with genetic changes that predispose to the early loss of eggs. In extreme cases, like most instances of Turner syndrome (these girls are born with only one X chromosome instead of two), the ovaries may not have any eggs at birth. In other instances, there may be eggs at birth but they then undergo an early decline leading to premature menopause. There are a wide variety of conditions and genetic mutations associated with an early decline in egg numbers; some examples are the Fragile X premutation, Galactosemia and BPES (Blepharophimosis-Ptosis-Epicanthus inversus Syndrome).

How can I protect my fertility?

At the present time, the most effective approach for preserving fertility is to freeze (or cryopreserve) sperm, eggs or embryos. Which one of these approaches is used depends upon individual circumstances.

Single men and women would typically freeze sperm and eggs, respectively. Clinical labs have extensive experience freezing sperm and it is a very effective approach for men to use before cancer treatment. There is less experience with freezing eggs, but major strides have been made with the development of newer freezing techniques known as vitrification.

If the woman is in a stable relationship, the favoured approach is to freeze embryos. This is because embryo freezing eliminates the uncertainties associated with post-thaw egg survival, egg fertilisation and subsequent embryo development.

For cancer cases, there is evidence that temporarily “shutting down” the ovaries using drugs known as GnRH analogues can protect eggs from chemotherapy. The evidence that GnRH analogues preserve ovarian function is strongest for breast cancer cases and GnRH analogues are now listed on PBS for this indication.

How do I go about freezing sperm, eggs or embryos?

Sperm freezing:
Freezing sperm is relatively simple and only requires a sperm sample to be produced through ejaculation. The sperm sample is then divided into smaller portions and frozen in liquid nitrogen at -196°C.

Egg freezing:
Freezing eggs and embryos requires an IVF-type procedure involving ovarian stimulation and an egg pickup. For egg-freezing, only mature eggs are frozen. For embryo-freezing, mature eggs are fertilised with sperm to make embryos, which can then be frozen on either Day2/3 or Day 5/6 of development. See my section on IVF/ICSI Treatment for more information.

Are there special considerations before undertaking fertility preservation in women diagnosed with cancer?

Yes, there are several important factors to consider.
It is important to weigh up the benefits of fertility preservation against any detrimental effects of delaying cancer treatment for 1-2 weeks.

Other considerations are how advanced the cancer is, the woman’s overall health at the time of diagnosis and whether she is well enough to undergo an IVF treatment cycle involving an egg pickup.

It is very important to consider the particular type of cancer involved. Breast cancer is the commonest cancer during the reproductive years and may have the potential to grow when exposed to the hormone, oestrogen. Because ovarian stimulation causes high oestrogen levels, it is important to undertake steps to prevent high oestrogen levels in women with breast cancer.

The other consideration is whether fertility preservation is even a feasible option; for instance, with extremely low ovarian reserve the very low chances of obtaining usable eggs or embryos may not justify delaying cancer treatment.

For more information on ovarian reserve, see my section on AMH, Ovarian Reserve and the “Egg Timer Test”.

It is also important to bear in mind that regardless of whether egg/embryo freezing is undertaken, the use of GnRH analogues should also be considered during chemotherapy.

As a woman, can I protect my fertility from the effects of ageing?

Some women may not be ready to start a family at an age when their egg quality is most conducive to supporting pregnancy; but in later years when they are ready, egg quality may have declined making pregnancy difficult or impossible. Women can therefore be faced with very difficult decisions. There aren’t any effective options currently available for reversing the effects of ageing on eggs after quality has already declined. The alternative is to freeze either eggs or embryos when egg quality is still good and to use these eggs later in life when the individual is ready to start a family.

The approach used for single women is to freeze eggs, often referred to in the lay press as “Social Egg Freezing”. Since age dictates the quality of eggs, the age at which eggs are frozen is the critical factor in determining how beneficial the approach is likely to be, as well as how many eggs would need to be frozen for achieving a reasonable chance of pregnancy down the track. Ovarian reserve (how many eggs the ovaries contain) is also a very important consideration since this will determine how many eggs might be obtained from a single round of ovarian stimulation. Some large companies like Facebook, Google and Apple pay for their female employees to freeze their eggs.

For more information on ovarian reserve, see my section on AMH, Ovarian Reserve and the “Egg Timer Test”.

Because embryo freezing offers more predictable outcomes than egg freezing, it would be preferable to freeze embryos if women are in a stable relationship.

Can fragments of ovarian tissue be frozen?

It is possible to freeze fragments of the surface of the ovary (known as ovarian cortex); this aspect of the ovary contains large numbers of ovarian follicles at the very immature (or primordial) stage (See my section on The Menstrual Cycle and Ovulation Tracking for more information on follicles). This approach is usually considered in females who are unsuitable for undergoing IVF to freeze eggs, for instance, young girls. However, this technique requires laparoscopic surgery to cut away pieces of ovarian tissue for freezing, which damages the ovary. At present, there are no effective means for developing the very immature follicles found in ovarian tissue outside of the body in the lab. This means that in order to use these immature eggs requires that the tissue be transplanted back in to the body. Obtaining eggs for pregnancy from these transplants then often requires an IVF procedure. There are very few centres in the world with extensive experience in utilising this technique.

Who can I see to explore my options for fertility preservation?

Based on the above discussion, it is clear that numerous factors need to be considered in each individual case in order to properly explore all the options available, as well as their feasibility, before embarking on any intervention for preserving fertility. This requires your specialist to have extensive experience and expertise in reproductive endocrinology, egg biology and IVF. Prof Homer is an international expert in how ageing affects egg quality. He recently published a comprehensive paper on this topic in the world’s top journal in reproductive biology. Prof Homer set up Queensland’s only research laboratory for studying eggs at the University of Queensland. His lab is understanding why ageing causes egg quality to decline and is developing new techniques for reversing poor egg quality. Prof Homer is also an expert in how drugs like chemotherapy bring about DNA damage that is responsible for the death of ovarian follicles. He is one of a handful of specialists in Queensland with the most advanced CREI qualifications for undertaking IVF and fertility preservation.