August 26, 2009

Fixing Mitochondria to Improve Invitro Fertilization (IVF) and Fix some Disease and Cheap IVF in Africa

1. The BBC reports that faulty mitochondria were successfully replaced in the eggs of monkeys and the eggs were fertilized and developed into healthy monkeys.

Faulty mitochondria effects about 15,000 babies every year and prevents some tens of thousands of women from having children. The US work, featured in the journal Nature, raises hopes of a treatment enabling women with defective eggs to have a child without using donor eggs.

The treatment would involve so-called "germ line" genetic changes which would be passed down through generations.

The genetic fault is contained in structures in the egg called the mitochondria, which are involved in maintaining the egg's internal processes.

If an egg with faulty mitochondria is fertilised the resulting child could have any of hundreds of different diseases including anaemia, dementia, hypertension and a range of neurological disorders.

US researchers have previously tried and failed to correct this defect by adding healthy donated mitochondria into the eggs of patients wishing to have children.

But these attempts resulted in birth defects - probably because mitochondria are so delicate that they are damaged when they are transplanted from one egg to another.

As a result, the treatment was banned by the US until it could be demonstrated that it was safe in animal experiments.

A group at the Oregon Health and Science University has now done just that.

They transferred the DNA needed to make a baby out of monkey eggs, leaving behind the potentially diseased genes in the mitochondria.

This was transplanted it into eggs emptied of DNA but containing healthy mitochondria.

The technique resulted in three healthy births with no sign of any birth defects.


2. New Scientist magazine reports that by the end of October, 2009, a clinic at the University of Khartoum plans to offer in vitro fertilisation to couples for less than $300, a fraction of its cost in the west.

Note: Lower cost but safe methods could be adopted to lower the general cost of healthcare in the west. This would be an important factor in the overall funding of public healthcare debate.

If successful, such efforts could lower the cost of IVF everywhere. In the US, the price of one round of treatment can be up to $12,000 and is rarely covered by health insurance. In the UK, it costs about £5000 ($8000), which the National Health Service may or may not pay for, depending on where a couple lives.




Some 10 to 30 per cent of African couples are infertile, often as a result of untreated sexually transmitted diseases, botched abortions and post-delivery pelvic infections.

stimulate egg production, many clinics in the west prescribe genetically engineered or "recombinant" forms of follicle-stimulating hormone (FSH) because it can cause women to release a dozen or more eggs per cycle. That means some embryos can be frozen in case the first round of IVF doesn't work. Such drugs have the disadvantage of being enormously expensive, sometimes costing thousands of dollars per round of treatment.

In contrast, clomiphene is a generic drug which prompts the pituitary gland to pump out more FSH and costs just $11 for one round of treatment. It was used very successfully in the early years of IVF, inducing maturation of up to four viable eggs per cycle. That's far fewer than with injecting FSH directly, but since low-cost IVF facilities are unlikely to have the equipment or liquid nitrogen for freezing extra embryos, fewer eggs are needed anyway.

Using clomiphene, the ESHRE group plans to transfer no more than two embryos to the woman's uterus, while the LCIF initiative plans to transfer only one.

Combined with not freezing extra eggs, this reduces the chance of a successful pregnancy, but as clomiphene has fewer side effects than recombinant FSH, women may be more likely try further rounds of IVF if earlier attempts fail. The ESHRE group estimates this will achieve a pregnancy rate of 15 to 20 per cent, lower than the European rate of 25 per cent and the US figure of 35 per cent.

Another big cost-saving has come in the use of incubators. Western doctors select the best embryos by allowing them to incubate for up to six days; those that fail to divide, or which show cellular defects, are then weeded out and the best transferred. But certain defects - multiple cell nuclei, for example - can be seen as early as the second day, and some embryos which fail in the artificial environment of a culture dish will develop normally in utero, according to Van Blerkom. On this basis, the ESHRE group plans to transfer the embryo on the first or second day after fertilisation.

Incubators themselves can also be made cheaper. Australian company Cryologic sells portable table-top incubators for less than $1000. These lack the fancy electronics and ability to change temperature of standard incubators, but this is unnecessary for IVF. Van Blerkom has used one to successfully incubate embryos and found that the batteries can be recharged with solar panels, also useful in countries where electricity outages are common. Meanwhile, the LCIF is counting on warm water baths to incubate embryos.

One company argues that incubators can be avoided completely, since a natural one - the woman herself - is already walking around. INVO Bioscience of Beverly, Massachusetts, recently launched the INVOcell, a small plastic capsule into which fertilised eggs are placed together with culture media. The capsule, encased in a protective shell, is then inserted into a woman's vagina for three days, which keeps the embryos at the desired temperature. After removal, doctors select the two best embryos and transfer them to the woman's uterus.

Company spokeswoman Katie Karloff claims that using the device - which costs between $85 in Africa and $185 in Europe - can cut the cost of IVF by half. It is also uniquely suited for places that frequently lose electrical power. Karloff reports that the INVOcell has now been used 85 times around the world, with 20 resulting pregnancies.

Cut-price $900 microscopes for confirming cell division can be easily adapted for minimal-cost clinics, says Van Blerkom, as can portable digital ultrasound machines that sell for less than $5000 - far below the typical $400,000 price tag for machines in western IVF clinics.




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