Female fertility has been back in the headlines recently. Kirstie Allsopp kicked things off back in June when she suggested young women should put their families ahead of their career aspirations because “fertility falls off a cliff” when they are 35. This was followed by the announcement this month that Apple and Facebook are to offer their female employees egg freezing as part of their health and wellness benefits from January next year. On top of this, a 36-year old Swedish woman became the first to give birth following a womb transplant when she was delivered by caesarean section in September.
Exciting times indeed. One wonders what the future holds, but also how safe and successful these procedures are and how common place will they become? Are these breakthroughs, which have taken years and years of research, likely to follow the path that IVF did and be mainstream treatment options or will they be reserved for a small minority that either need them or can afford them? And what about natural conception? Is that a thing of the past?
Let’s turn the clock back to June; of course Allsopp is right - female fertility does decrease with advancing age and as it falls pregnancy loss increases. As many as 40 per cent of all pregnancies end in miscarriage in women in their 40s. This reflects the link between egg number and egg quality both of which decrease as a woman ages. There is no ‘fertility cliff’ however, rather a gradual decline and, in fairness to Kirsty, this does become more apparent from 35.
But what exactly is fertility and why does it differ between women? Can it be maintained or even improved? Fertility is defined as the rate of childbearing in a population. It remains relatively stable up to 30 years of age with approximately 400 pregnancies for every 1000 women not using contraception for one year. It then begins to decrease until 45 years of age when only 10% of women will conceive not using contraception.
At the same time miscarriage rates steadily increase. Approximately 10% of women will miscarry at 20 years of age compared to 90% or more at 45 years of age or older. Half the couples not pregnant after the first year conceive in the second year leaving only 10% ‘infertile’.
It is recommended that a couple see a fertility expert for assessment after one year of trying and if all the tests are reassuring that they try for a second year. At that stage, if the couple has still not conceived, the best way to achieve a pregnancy, irrespective of age, is through IVF treatment. This does not mean that the couple cannot and will not conceive naturally, and many still do, but it is a more active way of moving forward and with proven efficacy. Investigations can be performed at an earlier stage if there are suspected problems. If the tests reveal blocked Fallopian tubes, significant endometriosis, and/or low numbers of poorly motile sperm then IVF is recommended without further delay.
IVF involves mixing eggs and sperm together in the laboratory (IVF) or the injection of a single sperm into a single egg (ICSI) to encourage fertilization. It is a very successful process but not perfect. If couples do struggle to conceive and require IVF the chances of success fall with advancing female age and more so from 35. Most couples require several attempts of IVF for each pregnancy, but interestingly many couples who go on to have unsuccessful IVF at this stage fall pregnant naturally in the months that follow.
Are some women more fertile than others and have more time? Are others less fertile and need to start the whole process even earlier? The answer to both questions is of course yes and so the next logical question is: are there any tests to measure these differences? There are tests to predict how a woman is likely to respond to the drugs used to stimulate the ovary in IVF, and to some degree how successful the treatment will be as there is a link between the number of eggs collected and the chance of having a baby.
These tests were developed for IVF prediction therefore and not to assess a woman’s fertility - but people are increasingly using them to advise women whether delaying childbearing is sensible or not and to predict when the menopause may occur. There are no robust studies to support such predictions and women and healthcare practitioners should be cautious in interpreting and extrapolating facts from studies predominantly undertaken in infertile women. Age, or more specifically female age, is the overriding factor for most couples and something we cannot ignore.
Taking all of this into consideration the best time for a couple to try for a family is when the woman is aged between 25 and 35 years of age. This decade seems to offer the best compromise between educational and fertility aspirations. Clearly this is neither appropriate nor opportune for all women but gives some guidance for those who have choice.
So what can women do if this is not the right time for personal, social or academic reasons? Well that’s where egg freezing comes in. Women have to go through the IVF process and have their eggs collected as they would if they were having treatment. Instead of the eggs being fertilized they are snap frozen and can be stored for several years. When they are defrosted they can be inseminated with the current partner’s sperm and the resultant embryos replaced as they are in conventional IVF.
Social egg freezing is not only increasingly in popularity but has also become more successful, with 80% of eggs now surviving the freeze-thaw process. The eggs maintain the quality they had when they were frozen and so reflect the age of the woman at that time.
Last week Apple and Facebook announced they are to offer a 'perk' of up to $20,000 (£12,000) to help women employees undergo egg-freezing and allow them to focus on building their careers. This has been met with much skepticism and suggestions the companies should be supporting women to have families at a younger age and their subsequent return to work in latter years. Whatever your viewpoint one cannot argue that choice has to be a good thing. Some experts suggest having 20 eggs frozen is enough to guarantee a pregnancy but this is far from true. There are no guarantees. It does offer hope and what was once considered only an experimental option for single women undergoing cancer treatment is now a real option for some women.
IVF and egg-freezing are not suitable for all women, however. Some women have limited egg reserves and can only produce poor quality eggs and therefore poor quality embryos. It’s too late to freeze eggs and the best option for these women is to have an egg from another woman, an egg donor. Women having treatment with donated eggs maintain the higher pregnancy rate seen in younger women (30-35%) because to be an egg donor you must be under 36 years of age. Women receiving donated eggs also have a much lower risk of miscarriage which highlights that it is the egg and not the womb that is the primary problem.
This brings us to the latest breakthrough, which is womb transplantation. After years of research and several attempts a woman in Sweden has given birth to a baby boy using a transplanted womb. The 36-year-old mother, who was born without a uterus, received a donated womb from a 61-year old friend. Once the womb had been transplanted and resisted rejection she had her own embryos replaced which had been created through IVF. She is not alone. Another eight women have had a new uterus and six are pregnant – an amazing 78% success rate. In contrast to the first case the donor of the wombs in most of these other cases is the woman's own mother, which means the same womb could carry two generations of the same family.
The procedure is not without risk. On this occasion the baby was born prematurely weighing 1.8kg (3.9lb) as the mother had to be delivered by caesarean as she had developed pre-eclampsia. It is also not a long term option as the women need to take immunosuppressant drugs to prevent the womb being rejected which are damaging in the long term limiting the window of opportunity as ultimately the new womb has to be removed.
Womb transplantation has not been developed to help older mums have babies but to help women who have either had to have a hysterectomy at a young age and those who are born without a womb. These women still have ovaries and therefore eggs and so are fertile. Their only possibility of a child of their own is through surrogacy which is not widely available.
So what about getting pregnant naturally, or are all babies to be created in the laboratory in 2050 in artificial wombs using eggs harvested years before? Of course not - how boring would that be! The figures above are reassuring and show that most couples will not experience any problems and even if they do take a bit longer than others the majority will fall pregnant within two years.
Is there anything couples can do to expedite this? Fertility, as we have seen, is influenced by many factors but the key ones are egg and sperm quality, tubal patency and the frequency of sexual intercourse. The best approach to maximizing ones chances are to avoid things that may have a negative effect on these factors. Lifestyle measures are increasingly being neglected but are very important. Smoking, excess alcohol and recreational drug use all negatively affect sperm and egg quality and possibly not only at the time but in the long term. Obesity increases infertility and miscarriage. A healthy diet rich in antioxidants and an active lifestyle are musts for all couples therefore. Women should take folic acid for at least three months before they start trying as eggs take this long to develop. The same is true for men as sperm take the same time to grow so take supplements such as zinc, selenium, and omega-3 alongside your partner.
What about checking if you are ovulating and timing when you have intercourse? There is no doubt that a woman needs be ovulating regularly if she is to conceive. For most women this is indicated by a regular menstrual cycle as 95% will be ovulating. Ovulation can be predicted by checking for the LH surge in the middle of the cycle or confirmed by measuring the levels of progesterone in the second half of the cycle (roughly a week before the period is due). There are numerous commercially available kits that can be used for both purposes. Do they help couples conceive though?
Some studies suggest couples that use these tests become anxious and that may actually impair their chances. Stress does seem to impair fertility but has no effect on pregnancy once established. If couples can use the tests to reassure themselves then they are likely to be helpful but if they are leading to anxiety then maybe they are best left on the shelf.
For most women with a regular cycle ovulation occurs two weeks before the next period is due. The egg lasts for around 36 hours and if not fertilized perishes. Sperm lasts for up to six days. If the time between repeated ejaculation increases the number of sperm increase but their motility falls. Ejaculating everyday will result in more motile sperm but lower numbers. Having sex every day or every other day from the end of the period (roughly day 6-7) up to the expected date of ovulation (day 14 for women with a 28 day cycle) and for a few days after should suffice.
So get out the running shoes, make sure you are having your five a day and, as hard as it may sound, try to relax.
For more information visit http://www.nhs.uk/IVF
Nick Raine-Fenning is Medical Director of Nurture Fertility and Reader of Reproductive Medicine & Surgery at the University of Nottingham