What do we do when we find no apparent cause of the infertility (less than 5%) or when we feel confident we are treating a problem or problems correctly but pregnancy is not forthcoming?

Before we can answer that question, we should review the sequences of events throughout the cycle that are necessary for a resulting pregnancy.

The first thing that happens after the period stops is that a cyst (follicle) starts to develop on one ovary or the other. This follicular cyst contains the egg and grows to about the size of an olive just before ovulation. Question: Are we sure there is an egg in the follicular cyst? Yes we are! You will not make follicles if you do not have eggs.

The next event in the sequence is that ovulation occurs. The cyst ruptures and the egg comes out of the ovary. Question: Are we sure that the egg gets out of the ovary at the time of ovulation. No! The only way we can know for sure that the egg was expelled is that pregnancy occurred that cycle. We know there is an uncommon condition called ‘ovum retention syndrome’ in which the follicle ruptures but the egg remains inside. All biochemical events will occur such as a rise in progesterone, elevation of the basal body temperature, etc. but the egg remains trapped inside the follicle. Although ovum retention syndrome is probably rare, we have no practical way of determining if this exists in an individual patient.

If the egg is extruded, the next order of events is ‘egg pickup’. Ordinarily, the fallopian tubes are laying down in the pelvis behind the ovaries. When ovulation begins, the fallopian tube on that side rises up out of the lower pelvis and moves and massages over that ovary. Once the egg is picked up, the tube falls off of the ovary and returns to its’ original location in the pelvis. We really do not have a clue why this happens. How does the tube know to do that? Question: Can we be sure that ‘egg pickup’ occurs. No! We can be sure the tubes are open (HSG x-ray) and we can be sure the tubes are free to move about in the pelvis (laparoscopy) but the only way we can be sure that egg pickup occurred is that if a pregnancy results in any given cycle.

If the egg is picked up by the tube, the next requirement is that sperm must reach the middle of the fallopian tube. Question: Can we be sure that sperm travel out into the tubes? No! With natural intercourse, sperm need to swim out of the ejaculate, at the top of the vagina, into the cervical mucus and then be transported through the uterus and into the tubes. We can perform a post coital or Huhner test after intercourse to see if sperm are living in the cervical mucus, but this test does not prove that the sperm arrived in the tube. Even with intrauterine insemination, we cannot be completely sure the sperm reached the mid-tube. Again, only if a pregnancy resulted can we be sure that sperm were in the fallopian tube.

After sperm have reached the fallopian tube, the next step is fertilization. Question: Can we be sure that fertilization occurred? No! Only if a pregnancy resulted can we be sure.

If fertilization occurs, the next step is implantation. Question: Can we be sure there is/is not a problem with implantation? No! Implantation into the lining of the uterus (endometrium) occurs three to five days after ovulation. We believe that the endometrium should be at least 9 mm. thick and the blood progesterone level should be between 10-15 ng/ml. for proper implantation to occur. Although we can measure the endometrium by ultrasound and we can obtain a blood progesterone level, we still cannot prove implantation unless there is a resulting pregnancy that cycle. The implantation phase is probably the most poorly understood of all the steps required leading to a pregnancy.

Wow! It’s a miracle that anyone achieves a natural pregnancy.

Now, let’s go back to the original question. What do we do next if we can find no cause for the infertility or what do we do if we know specific treatments are ‘working’ but pregnancy has not been forthcoming within three “good cycles”? The logical next step is in vitro fertilization (IVF). With IVF we know the eggs got out of the ovary because we take them out. We have no need for the tubes to pick up the egg and, in fact, we don’t even need the tubes. We don’t care if the sperm get to the fallopian tubes because the sperm and eggs are placed together in a dish. We know fertilization occurs because we can see it under the microscope. We know the embryos reached the endometrium because we put them there at the time of embryo transfer. The only step we still cannot know about is implantation.

There are probably many more requirements to achieving pregnancy, but this is what we know now. Over the years, our understanding will improve and new tests and techniques will be developed. If you are interested in reading more about IVF, please go to that section.

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