Controlled Ovarian Hyperstimulation
or
Superovulation

Treating couples with major infertility problems is easy and straightforward. The results may be disappointing but the decision making process is simple. A woman with severe endometriosis or severe tubal damage requires surgery. A woman who does not ovulate at all requires Clomiphene or Pergonal*. If the husband is sterile or very infertile, donor insemination is often necessary.

There exists, however, a sizable group of infertile couples with relatively minor problems who still do not conceive. Often the women have early stage endometriosis. The husband may be subfertile but still has semen quality in the range that is compatible with fatherhood. Various names have been given to this problem but the one I favor is "Minimal Abnormality Infertility" or MAI. These are couples who can not be labeled as "unexplained infertility" (a very rare problem in my experience) but whose problems are such that a pregnancy should occur but does not.

Some physicians do use the term "Unexplained Infertility" in such instances. By this, they mean that even though the couple may have problems, the severity of those problems is not enough to "explain" the infertility.

The issue of what to do with MAI patients has long been area of uncertainty and debate. However, with all the data that has been accumulated over the past 10-15 years, we have a much better understanding of what therapies work best with such couples.

In the early days of In Vitro Fertilization, there were very few programs. Those few programs had very long waiting lists. These IVF programs were looking for something to do with couples who were in the pipeline waiting to begin therapy. Often, MAI or unexplained infertility couples were put on Pergonal for want of something better to do until their number came up. It was quickly discovered that many of these couples achieved a pregnancy on Pergonal alone when other, more traditional therapies had not worked previously.

When semen is prepared for IVF or GIFT, it is put through a process called semen enhancement, whereby the good, motile sperm are separated from the dead or poorly motile sperm. The semen is first washed and then the "good" sperm are separated from the dead sperm and debris. Several different techniques are used but all employ the same basic principles. What is important is not only to separate the good sperm from the poor quality sperm but also to eliminate the various hormones and other chemicals found in "raw" semen.

After the semen is processed, the improved or "enhanced" semen can be placed directly inside the uterus - a procedure called Intra-Uterine Insemination, or "IUI". It is important to understand that simply putting natural semen into the cervix is a totally useless therapy. I am aware that many women have been put through this type of therapy but please understand that it is a waste of time and money. All that putting the husband's semen into the cervix does (with rare exceptions) is substitute for intercourse and does nothing to improve pregnancy rates. Except for rare, special instances, putting the husband's semen into the cervical mucus has no place in modern infertility therapy.

Over the past few years, an attempt has been made to achieve pregnancies using a combination of deliberate ovarian hyperstimulation using Clomiphene or Pergonal combined with IUI. The current debate is whether this Controlled Ovarian Hyperstimulation (COH) or "Superovulation" as it is sometimes called combined with IUI is a valid therapy for the couple who has undergone all other traditional therapies and who have still not achieved a pregnancy. There is a great deal of literature on this but the final answer (as of 1999) is still not in. I will try to summarize the data as best I can but it is often still unclear.

There is no doubt that if the woman has poor cervical mucus or if the post-coital test is persistently abnormal, IUI does make a difference. There is also good evidence that for couples with MAI or true unexplained infertility, COH / IUI does offer a good alternative to IVF / GIFT / ZIFT, etc. The pregnancy rates are equivalent and couples who fall into these categories should try COH / IUI before going on to the more involved procedures, if for no other reason than recent studies have shown the pregnancy rates to be about the same and the cost of COH/IUI is substantially less.

The current dilemma (as always in the field of infertility) is whether or not COH / IUI offers any advantage for the couple where a male factor is the primary problem or is playing a significant role. Since the effective treatment of the infertile male remains the last great hurdle in infertility, you can understand that the current medical literature is still divided as to how effective this therapy is. Some studies show a definite improvement in the pregnancy rates whereas others show no difference. There is some evidence that it may depend on how severe the male factor is. Those men with milder impairment seem to benefit from COH/IUI; if the male factor is severe, probably little will help. Success rates for IVF or GIFT are also lower when a male factor is present. Some preliminary studies suggested that 2 IUI's per cycle may improve the pregnancy rate, but more recent studies did not show any significant increase.

The other debate is whether it is the COH or the IUI or both that makes the difference. Most infertility specialists feel that the COH is principally responsible for the improved pregnancy rates but the IUI doesn't hurt and probably helps. The problem is that most of the studies demonstrating an increased pregnancy rate with COH / IUI are not properly controlled. I have seen very few randomized studies. However, a recent paper from Italy did demonstrate that COH / IUI was better than COH alone and the control group was comparable to the study group. On the other side of the coin, a well controlled study could not demonstrate that IUI improved pregnancy rates.

A recent study in the New England Journal of Medicine published in early 1999 did show that for many couples, COH / IUI does help, but again, if there was a severe male factor, the improvement in pregnancy rates was not as dramatic as when the man bad a normal semen analysis.

Another technique involves placing the prepared semen directly into the Fallopian tube through the uterus using a small plastic cannula. This is done under ultrasound guidance. Again, it is too soon to know whether this will offer any advantage. It may offer a definite advantage in those situations where the woman has 2 ovaries but only one good tube. Directed IUI may allow placement of the sperm only on the "good" side.

In summary, for the couple who has gone through all the usual therapies and has not established a pregnancy, COH / IUI offers a reasonable and often effective alternative to IVF or related procedures. This is particularly true if early endometriosis or other less severe problems are the cause of the infertility. It is also true if the infertility problem is of long duration. Couples with infertility of less than 3 years duration do not seem to get as much benefit although it is still a worthwhile procedure.

COH / IUI also offers a good alternative to any couple seriously contemplating IVF unless there is virtually no hope of a pregnancy occurring otherwise. COH / IUI may also be paid for by insurances (or at least a portion will be) whereas IVF is usually excluded. Many couples therefore choose COH / IUI for financial reasons. Unfortunately, more and more insurance companies are refusing to pay for IUI, thereby further hindering an infertile couple's ability to have a baby. However, the cost of IUI is still substantially less than IVF.

The only unanswered question as this time is how effective this therapy will be as a treatment for male factor infertility.

*Pergonal was the first of the injectable infertility drugs. Now, there are many including Humegon, Metrodin, Repronex, Follistim, and Gonal-F. Rather than list all of them each time, I will use "Pergonal" as a generic term. Most of the comments in this pamphlet apply to any of them, with occasional exceptions as mentioned.