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, adopting the "never mind the cost" attitude. 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 without maintenance and after-sales services to keep them functioning properly, the result is that these systems often become white elephants.
IVF has developed and evolved 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, they are not relevant in the developing world, where the basic goal of an IVF clinic is to provide service for infertile patients. The other direction in which IVF is evolving is towards simplification. While it is true that these "simplified IVF techniques" do not 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. However, superovulation does not just carry the risk of ovarian hyperstimulation carry the risk of ovarian hyperstimulation (a potentially life-threatening condition in which the ovaries become very enlarged because of the multiple follicles), but it also carries the risk of multiple pregnancies and the related problem of what to do with the unwanted eggs and embryos. Therefore, a number of clinics are now returning to the "natural," unstimulated cycle for IVF, which is much less expensive! (1) Many clinics are also finding that using clomiphene for gentler ovarian stimulation gives good results for younger patients. Since most women in developing countries get married young, the average age of infertile couples is much less in India than it is in the West, making these protocols much more suitable for Indian conditions.
The major problem with the original natural cycle protocol was that doctors used to wait for the spontaneous LH surge. This meant frequent monitoring for LH levels, 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 a physician to time the egg pickup during the day. IVF is now turning full circle - remember, the egg of the first test-tube baby was in fact recovered in a "natural" cycle. The only disadvantage of this method is that the cancellation rate of treatment is higher, because some eggs will ovulate before the time of egg retrieval.
A good IVF programme needs laboratory services of high standard to ensure that the eggs, sperm, and embryos are maintained in an optimal environment in vitro. This has been the major stumbling block for most IVF programmes. The major limiting factor to providing IVF services has been the availability of IVF laboratory expertise. The method of transport IVF, as described by Kingsland (2), 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, ensuring high quality. Since all laboratory procedures are performed in a central IVF laboratory, it also allows one IVF laboratory to obtain the necessary experience and expertise that is so important for maintaining high pregnancy rates.
Commercial culture medium
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, Scandinavian IVF, Menezo B2, Medicult IVF Medium, and Human Tubal Fluid - IVF programmes no longer need to make their own culture medium, as it can now be bought "off the shelf." This has helped to minimize the possibility of poor quality culture medium, which used to be the major challenge responsible for reducing pregnancy rates in IVF programmes in the past.
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. (3) Basically, in IVC 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, but 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. (4) 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 in this area is currently underway.
While the standard technique for women with blocked tubes has been IVF, the method of GIFT (gamete intrafallopian transfer) developed by Asch (5) 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 tubes provide a more physiological milieu for the gametes. GIFT also requires less laboratory expertise than IVF, since in vitro gamete handling 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 (6) has 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 serving to reduce its expense.
Our personal philosophy towards assisted conception (7) is to try to keep it as simple and cheap as possible. We are willing to accept lower pregnancy rates per attempt, but since our patients can afford many more attempts, our cumulative conception rate is quite good. If the cost-effectiveness of treatment is considered (the number of 'take-home babies' per dollar spent) then our cost-effectiveness is 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, our approach makes IVF services available to couples who could never have even dreamed of making a single attempt in any other centre because of the high expenses 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. On the other hand, if treatment was simple and inexpensive, patients could be counseled to view each attempt much as an insemination cycle is viewed today - something to be repeated as needed until the goal is reached. Aside from providing an additional alternative for most patients, this offers a much more realistic option. This would reduce stress and anxiety considerably, and make treatment much more manageable for the patient.
Present-day IVF research in is focused on high-technology areas - for example, microinjection of sperm. These techniques are very expensive, applicable to few patients, and have poor pregnancy rates - they have reached the point of diminishing returns. Instead, IVF research today should focus on the further development-assisted conception, whereby better pregnancy rates can be achieved.