Monday, December 21, 2015

Forever Young--------- Secret to fountain of youth using ovarian tissue transplant to stall menopause



The dramatic increase in average life expectancy during the 20th century ranks as one of society’s greatest achievements. Most babies born in 1900 did not live past 50! But currently worldwide, the average life expectancy at birth is 71.0 years (68.5 years for males and 73.5 years for females) over the period 2010–2013 according to United Nations World Population Prospects.

Japanese women took the top spot in average life expectancy worldwide for the third consecutive year by living up to average age of 86.83 years. Women, who tend to outlive men, will comprise the bulk of the older adult population and it is predicted that women will live up to 100 by the year 2055.

According to National Institute on Aging, the “oldest old” (people aged 85 or older) constitute 8 percent of the world’s 65-and-over population: 12 percent in more developed countries and 6 percent in less developed countries.

Assuming the median age for the onset of menopause is 51; women will spend about 40 years in menopause deprived of naturally produced oestradiol and progesterone, leading to an increasing incidence of menopause-related disorders such as osteoporosis, dementia, neuromuscular degenerations, cardiovascular diseases and lack of general well-being.

Currently, exogenous oestradiol is being used in its various forms as a preventive as well as curative modality.

This article by Andersen  C.Y and Kristensen S.G in August issue of Reproductive Bio-Medicine Online  discusses a radical new method to postpone menopause. It is based on the hypothesis that ovarian cortical tissue freezing in order to permit future transplantation can become a possible option for a great number of women for postponing menopause and thus alleviating its sequelae.

The surplus ovarian follicles in youth could be cryopreserved, to be used after natural menopause

Currently the main use of ovarian tissue preservation is to preserve the fertility in patients with malignancy  but the endocrine potential of the preserved cryo tissue can be exploited for a more physiological solution to menopause related medical problems.

This appealing technology is already available, but it is to be seen whether it works to postpone menopause, possible in those patients who already have done ovarian preservation.

The ovaries of a newborn female contain a million eggs in the form of resting follicles. An average women will ovulate on an average 450 times from puberty to menopause, the rest 99.9% of eggs will undergo degeneration.
Many of the follicles constituting this enormous loss possess the ability for growth and development and hence sex-steroid secretion, but may not contain oocytes best suited for reproduction.

It is also known that a woman with one ovary is as fertile as women with both the ovaries, according to a large study by Lass et al, 1997 in Journal of Human Reproduction.

Two large studies by  (Bjelland et al, 2014, Yasui et al, 2012) also proved that the age of menopause is only one year earlier for women with one ovary as compared to her normal counterpart.

All the information about safety and efficacy of the re-transplanted ovaries comes from patients affected by cancer who cryopreserved ovarian tissue prior to gonadotoxic insults (chemotherapy or radiotherapy).

It is seen that menstruation cycle is reestablished in most patients with a clinical pregnancy rate of 30% is achieved.

Current experience from the author’s center shows that the re-transplanted ovaries functioned normally for 6-11 years. .

It is noticeable that tissue in these patients has been transplanted with the intention of providing fertility, which requires a larger pool of follicles (i.e. more tissue) to be transplanted than for providing menstrual cycles alone. Therefore the longevity of this tissue if the aim was to postpone menopause would probably be longer.

In addition, ovarian tissue will start to work in most places in the body and may be transplanted subcutaneously during local anaesthesia. In this way natural fertility will be avoided and will prevent senior women from becoming pregnant.

The risks associated with extending the menstrual cycle past the age of natural menstrual cycles may augment the risk for cancers like breast cancer? In recent years much of the risk of breast cancer due to MHT has been alleviated. What about the uterus and the cervix? Should hysterectomy and mastectomy be a part of ovarian transplantation to treat menopause in order to reduce the late-onset risks of cancer?

Careful consideration, individually tailored advice and close monitoring are needed for women who may want to use their ovarian tissue for postponing menopause.

Thousands of women worldwide have already had ovarian tissue frozen for fertility preservation due to different malignancies. For various reasons, a large number of these women will not have used their tissue by the time they reach menopause, either prematurely or at the expected time of menopause and will have tissue available for continued ovarian function. Some of them might want to use it for postponing menopause. They will indeed have this opportunity available without experiencing additional risks and may represent a group of patients in which initial results can be obtained.

Furthermore cryopreservation of isolated human pre-antral follicles is now also available which implies that a predetermined number of follicles may be transplanted in small alginate beads just a few microlitres in size.

Currently, the only use of ovarian cryopreservation is for fertility preservation, but in near future transplantation of frozen-thawed ovarian tissue may serve as a physiological solution to prevent the massive medical legacy of osteoporosis and other menopause-related disorders in the ageing population.

The unanswered questions at present are i) Does the grafted tissue carries a higher risk of malignancy? (ii)The functional integrity of the tissue in women who are menopausal? and (iii) How many women will be attracted to postponed menopause, with continued menstruation?

It is also thoughtful to think of other aspects of this procedure such as these patients sometimes have other co- morbidities that must be taken into account. Access to healthcare will be another challenge as well as whether it will be covered by insurance or not?

If proven successful, will it save billions of dollars in healthcare spending due to morbidities of menopause like CVD and osteoporosis?

The aim of this article was to open up a discussion about the new endeavor of technical opportunity to postpone menopause further? In the future, will it be possible to utilize the enormous loss of human follicles that naturally occur to avoid menopause for prolonged periods of time?

In principle the authors see no reasons why ovarian transplants to treat menopause ought not be pursued. But before going forward a large number of issues need to be addressed and the foremost is to show this form of transplantation is really a useful tool in alleviating the debilities associated with menopause without causing or exacerbating other health risks.

Only then it could be offered as therapy!


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