Beating the female biological clock

To boost the fertility rate, Singapore should reconsider its ban on social egg freezing and allow the three-parent technique

The menopause and female biological clock are unique oddities in humans, compared with other animal species. One popular scientific theory of its origin is that the menopause evolved to enable longevity in older women so that they can contribute to the upbringing and survival of their grandchildren, and serve as a mental repository of accumulated tribal knowledge during the Stone Age when writing was non-existent. Back then, before the advent of modern medicine, pregnancy and childbirth were extremely risky and frequently led to high mortality rates among women.

In the modern era, however, the biological clock has become a tremendous liability for women, who are now expected to be educated, develop careers and compete equally with men in the global marketplace. This is particularly apparent in Singapore, where the increasing trend of late marriages and motherhood has brought about a fertility crunch due to the rapid decline in the quality of a woman's egg reserve beyond 35 years of age.

Currently, there are two promising techniques that can enable older women to beat the biological clock and beget their own genetic offspring. One of these, social egg freezing - that is egg freezing for non-medical needs - has already been intensively debated in Singapore, but still remains banned by the Ministry of Health (MOH). The other technique, mitochondria replacement therapy, better known as the three-parent technique, will be openly discussed in an upcoming public consultation by the Bioethics Advisory Committee.

Although the recent hype over the three-parent technique was focused on preventing transmission of genetic diseases, it was, in fact, originally developed for the treatment of female infertility. The recent scientific breakthrough by Dr John Zhang in Mexico involved complete mitochondrial replacement. Prior to that, about two decades ago, partial mitochondria replacement with the three-parent technique was pioneered by Dr Jacques Cohen at the Saint Barnabas Medical Centre in the United States, for improving the egg quality of women with repeated in-vitro fertilisation (IVF) failures. In both cases, donated eggs from a "third parent" were utilised.

From 1996 to 2001, a total of 17 children were born from the three-parent technique, before a ban on the procedure was imposed by the US Food and Drug Administration in 2001. At a recent press conference initiated by Dr Cohen to allay public concerns over the safety of this technique, it was revealed that all 17 children are currently healthy and doing well at school.


The writer highlights two techniques that can enable older women to beat the biological clock and beget their own genetic offspring: social egg freezing and mitochondria replacement therapy, or the three-parent technique. He says both are complementary to each other in boosting the fertility rate in Singapore. ST PHOTO: EDWARD TEO

The pertinent question that therefore arises is whether it is ethically justifiable to permit the use of the three-parent technique for fertility treatment of older women (without any genetic diseases), while at the same time banning social egg freezing. After all, is it not the ban on social egg freezing that would drive some older women to resort to such a complex, expensive and ethically controversial treatment procedure?

In a more recent breakthrough by Dr Shoukhrat Mitalipov at the Oregon Health and Science University in the US, the three-parent technique was used to double the number of eggs collected for IVF patients by combining the genetic material of egg leftovers (polar body) from the patient, with eggs derived from a healthy donor.

Hence, the three-parent technique can be a viable alternative to social egg freezing for beating the biological clock in older women, by overcoming age-related decline in egg number and quality. In fact, because genetic diseases are relatively rare, while poor egg quality in older women is commonplace, it is anticipated that the major application of the three-parent technique, if approved in Singapore, would be predominantly focused on the treatment of infertility in older women.

The pertinent question that therefore arises is whether it is ethically justifiable to permit the use of the three-parent technique for fertility treatment of older women (without any genetic diseases), while at the same time banning social egg freezing. After all, is it not the ban on social egg freezing that would drive some older women to resort to such a complex, expensive and ethically controversial treatment procedure? By permitting social egg freezing, would not the number of patients seeking to undergo treatment with the three-parent technique be reduced?

Moreover, the three-parent technique also imposes additional health risks to a second party in the form of an egg donor, unlike social egg freezing which does not require an egg donor. It must be noted that the race or ethnicity of egg donors do not really matter for the three-parent technique, as the donor contributes only about 0.1 per cent of her DNA, and would influence neither the physical features nor complexion of the conceived child. Hence, the pool of potential egg donors for the three-parent technique can be broadened to include women of all races and ethnicity. This could likely result in a higher demand for impoverished foreign egg donors by Singaporean patients, with the attendant risks of illicit under-the-table payments and undue involvement of foreign egg donation agencies.

Another ethical issue is the reduced chances of conception for patients undergoing the three-parent technique, as compared with conventional egg donation. If the patient is going to spend so much money on medical fees and expend so much effort in sourcing scarce donor eggs for her own treatment, she should rightfully be counselled and informed of this fact, prior to deciding whether it is worthwhile taking the extra risk with the three-parent technique to beget her own genetic children. Would she be better off, if she had instead opted for conventional egg donation?

Also, many of the arguments put forward by the MOH in its decision to ban social egg freezing in Singapore are also applicable to using the three-parent technique for fertility treatment of older women without genetic diseases.

Like social egg freezing, the three-parent technique is neither a guaranteed nor reliable path to parenthood for older women. Arguably, this technique may also give a false sense of hope and security to both single women and married couples, which could in turn further exacerbate the trend of late motherhood with the associated risks of pregnancy complications in older women. Hence, there would be inconsistent and misaligned policy formulation if the MOH were to approve the use of the three-parent technique for treatment of infertility in older women without genetic diseases, while at the same time retaining the ban on social egg freezing.

Indeed, to boost the fertility rate of Singapore, social egg freezing and the three-parent technique can, in fact, be complementary to each other.

For example, the major challenge faced by the clinical application of the three-parent technique is the procurement of scarce donors eggs in Singapore, where there are stringent regulations against payment for egg donation. This problem may be overcome if social egg freezing were to be permitted, which would result in an accumulated surplus of excess frozen eggs that can potentially be donated to older women undergoing the three-parent technique. It is anticipated that women would be more psychologically comfortable with donating their excess eggs, if they knew that they are going to contribute only about 0.1 per cent of their DNA to the child conceived by the three-parent technique.

On the other hand, the major challenge faced in social egg freezing is that most women freeze their eggs when they are too old, when the quality of their eggs has severely declined. The high costs of egg freezing deter many women from undergoing the procedure at younger ages when their egg quality is optimal.

This problem can be overcome if patients undergoing the three-parent technique are willing to financially sponsor social egg freezing for younger women, in return for the donation of some of their eggs, thus leading to a win-win situation for both parties concerned. Indeed, this is currently a widespread practice in British fertility clinics, where it is commonly referred to as "Freeze and Share".

Hence, for a more consistent and aligned policy direction in the regulation of new reproductive technologies in Singapore, the MOH should also permit social egg freezing if it were to permit the use of the three-parent technique for fertility treatment of older women without any genetic diseases. Either this, or MOH should ban both techniques together. It would be a fallacy to permit one of these techniques to overcome age-related female infertility, while banning the other.

• The writer is a stem cell scientist based at the University of Hong Kong. He had previously worked in the field of human reproductive medicine research in Singapore.

A version of this article appeared in the print edition of The Straits Times on December 20, 2016, with the headline 'Beating the female biological clock'. Print Edition | Subscribe