IVF and related assisted reproductive technologies (ART) offer great hope to infertile couples the world over. Because these techniques are so expensive, however, they are out of the reach of the vast majority of couples - and especially of those in the developing world. This is because IVF programmes are too technology-intensive at present - and anything which is complicated is bound to be expensive.

A high-tech approach is especially counterproductive in the developing world, where doctors usually blindly duplicate what foreign IVF programmes do. They imitate the Western ideal that is so tempting with its sophisticated equipment - ‘never mind the cost’. If this approach were successful, then there would be little to criticize, but it can never be practical because the infrastructure to support such sophisticated services is simply not available in the developing world. Thus, for example, it is easy to buy an imported CO2 incubator or a reverse-osmosis water-preparation system - but with just no maintenance and after-sales services to keep them functioning properly the result is that these systems often become white elephants.

IVF has developed in two different directions today. One is the high-tech approach, which includes such glamorous techniques such as microinjection, pre-implantation genetic diagnosis, and embryo co-cultures. These’ second generation IVF procedures’ are very expensive and labour- intensive, however; they are applicable to few patients; and while worthwhile in advanced IVF laboratories in the West, are not relevant in the developing world, where the basic goal of an IVF clinic service to infertile patients.

The other direction in which IVF is evolving is towards simplification. While it is true that these ‘ simplified IVF techniques’ do not as yet offer as good a pregnancy rate as conventional IVF, they are much more relevant in the developing world. What have these simplifications been?

A major expense of the IVF cycle is the cost of the gonadotropin injections used to induce superovulation. Superovulation using GnRH (gonadotropin - releasing hormone) analogs and hMG (human menopausal gonadotropin) has now become the norm for most clinics, since stimulated cycles produce more eggs and therefore more embryos and a higher pregnancy rate. Not only, however, does superovulation carry the risk of ovarian hyperstimulation carry the risk of ovarian hyperstimulation (a condition in which the ovaries become very enlarged because of the multiple follicles, which can be potentially life- threatening), but also the risk of multiple pregnancies and the related problem of what to do with the unwanted eggs and embryos. A number of clinics are therefore now returning to the ‘natural’ unstimulated cycle for IVF - which is much less expensive!

The major problem with this protocol was the need for frequent blood or urine tests for LH (luteinising hormone) to determine egg maturity; and the need to be ready to do egg pickups at all hours of the day or night. However, newer protocols using the natural cycle allow ovulation to be induced with hCG (human chorionic gonadotropin), which in turn allows one to minimize LH monitoring, and also to time egg pickup to be during the day. IVF is now turning full circle - remember, the ovum of the first test - tube baby was in fact recovered in a ‘natural’ cycle.

A good IVF programme needs laboratory services of a high standard to ensure that the eggs, sperm, and embryos are maintained in an optimal environment in vitro, and this has been the major stumbling block for most IVF programmes. The major limiting factor with providing IVF services has been the availability of IVF laboratory expertise. The method of transport IVF offers a very attractive solution to this problem. Basically, this means that egg pickups are performed in peripheral clinics and hospitals; and the husband transports the follicular fluid (with the eggs) to the central IVF laboratory using a specially designed incubator which runs off the car battery. All IVF laboratory procedures, and later the embryo transfer, are carried out in the central laboratory.

This method allows gynecologists to take an active part in their patients’ treatment, ensure high quality, since all laboratory procedures are performed in a central IVF laboratory, and also allows one IVF laboratory to obtain the necessary experience and expertise that is so important for maintaining high pregnancy rates.

Making IVF culture medium in which the eggs and embryos are nourished in vitro is a major problem. Not only is very expensive equipment needed to produce this medium, but scrupulous quality control and testing is needed to ensure that each batch can maintain embryo growth. With the recent commercial availability of quality-controlled and tested culture medium - for example from Medicult and Scandinavian IVF, IVF programmes no longer need to make their own culture medium, as this can now be bought ‘off the shelf’. This has helped to minimize one of the variables which used to reduce pregnancy rates for IVF programmes - toxic culture medium.

Incubating the eggs and embryos in vitro requires expensive CO2 incubators, which must maintain just the right environment for the embryos for long periods of time. The method of intravaginal culture (IVC), however, allows one to provide IVF services without using a CO2 incubator and is an extremely attractive alternative. Basically, in IVC5 the eggs and sperm are placed in culture medium in a sterile vial which is hermetically sealed and then placed in the woman’s vagina where it is held in place with a vaginal diaphragm. This means that the woman acts like her own IVF incubator and keeps her embryos at the right temperature -- 37° C . This method requires less handling of eggs and embryos and provides a fertilization rate comparable to that of conventional IVF - at much less expense.

Perhaps the ultimate simplification in IVF is the method of transcervical oocyte-sperm transfer. As the name suggests, this simply involves transferring the eggs (oocytes) and sperm back to the uterine cavity through the cervix after egg pickup. The rationale behind this method is that fertilization will take place in the uterine cavity and the resulting embryo will then implant here. While studies of this procedure have been very preliminary, much research work is going on in this area.

Another innovation in this field has been the concept of encapsulated gamete intrauterine transfer in which the eggs and sperm are transferred into the uterine cavity after placing them in a biodegradable semipermeable matrix. The capsule acts functionally like a temporary incubator chamber which prevents the egg from being damaged as a result of direct contact with the endometrium. After fertilization has occurred in the cavity, the capsule dissolves and releases the embryos for implantation. If this technique lives up to its promise, then many more centres will be able to provide assisted conception services to their patients.

While the standard technique for women with blocked tubes has been IVF, the method of GIFT (gamete intrafallopian transfer) developed by Asch is the method of choice for women with non-tubal infertility. In this method the eggs and sperm (gametes) are transferred directly into the fallopian tubes (which is where they ‘belong’). Pregnancy rates with GIFT are higher than IVF because the human fallopian tube provides a more physiological milieu for the gametes. GIFT also requires less laboratory expertise than IVF since gamete handling in vitro is minimized. A major limitation with GIFT was the need to perform a laparoscopy in order to transfer the gametes into the tubes. However, Jansen has now developed special catheter sets that allow the gametes to be introduced into the tubes under ultrasound guidance - thus making ‘vaginal GIFT’ a non-surgical procedure and reducing its expense.

In developing countries, IVF clinics need to try to keep IVF as simple and cheap as possible. They should be willing to accept lower pregnancy rates per attempt, but since patients will be able to afford many more attempts, the cumulative conception rate will be quite good. If the cost-effectiveness of treatment is considered (the number of ‘take-home babies’ per dollar spent) then the cost-effectiveness is likely to be comparable to the best in the world. While it may be true that patients may take longer to get pregnant, they spend much less money in the long run. Most importantly, this approach will make IVF services available to couples who could never have even dreamed of making a single attempt because of the expense involved.

Simplified protocols are also much more ‘patient-friendly’. Since conventional IVF is so expensive, going through the process is very stressful for patients. The monitoring is very intensive and disrupting. Since so much money is at stake, patients are very apprehensive of the outcome, and are distressed if the cycle fails.

Moreover, since the treatment cycle is so expensive, few patients can afford to repeat it - so most have to drop out without succeeding in getting pregnant. If on the other hand, treatment was simplified and inexpensive, patients could be counselled to view each attempt much as an insemination cycle is viewed today - something to be repeated as needed, till the goal is reached. This is a much more realistic option for most patients - and one more of them. This would reduce stress and anxiety considerably, and make treatment much more manageable for the patient.