Virtual Azoospermia and Male Infertility
Introduction to Virtual Azoospermia
Virtual azoospermia, which denotes a very low sperm count, can be described in several different ways. The most common way is perhaps the estimated number of sperm per cubic centimeter—for example, 100,000 sperm per cc (also written as 0.1 × 106/cc). You may also see this written as number of sperm per high-power field (HPF). For example, with an uncentrifuged specimen, you might see “3 sperm seen on entire slide” or “3 sperm seen on Makler” (the Makler chamber is the counting chamber used to measure the sperm count and motility in one drop of semen). When a centrifuged (that is, concentrated) specimen is examined, you might see a report like “8 sperm seen in centrifuged specimen, 2 of which were motile”- now this does not mean that there were just 8 sperm in the entire ejaculate, just the number of sperm in that drop (and there might be 50 drops or so in the entire specimen depending on how it was processed). Of course, only 8 sperm seen in a drop of the concentrated specimen is going to represent a more severe problem than 8 sperm seen in only one drop of the (unconcentrated) semen.
The current guidelines for genetics testing include a sperm count under 2.5 million sperm/cc, so men with virtual azoospermia fit into this category (unless they have another known source of their sperm production problems, such as prior chemotherapy). Please see the "Genetics" section for more information.
Are There Enough Sperm for IVF/ICSI?
Patients with virtual azoospermia can sometimes have such low sperm counts that not enough sperm are present to proceed with IVF/ICSI. The lab that is planning on doing the IVF should have its own technicians evaluate the semen and decide whether they think there is enough sperm to inject all of the eggs they anticipate retrieving. This decision is made in consultation with the IVF doctor, who can often roughly estimate the number of expected eggs based upon the woman’s age and ovulatory reserve.
Freezing of Sperm for Men with Virtual Azoospermia
Freezing (cryopreservation) of sperm is always a good idea in men with sperm counts of under 1 or 2 million sperm/cc. In this case, if enough sperm are not present on the day of IVF egg retrieval, then the lab can thaw out the backup frozen sperm to use. Another option would be to freeze (vitrify) the eggs for later use
The problem with sperm cryopreservation, however, is that approximately 50–75 percent of sperm do not survive the freeze-and-thaw process. (In better-quality specimens, higher percentages of sperm typically survive being frozen.) Freezing good numbers of sperm is generally not a problem in men with higher sperm counts. However, sperm from men with virtual azoospermia typically do not freeze well, and with such men the thawed semen specimen may not yield any sperm that are alive and usable for IVF. The IVF lab needs to decide, based on the sperm density and quality of a particular fresh specimen, whether they think they will be able to retrieve sperm after the freeze-thaw process for that specimen. It’s important to realize that relative sperm quality can change from sample to sample in the same person, since every man’s semen parameters fluctuate from week to week, so providing several specimens for preservation may be necessary for the lab to make this determination. Some labs freeze a smaller test sample, which they can then thaw out to check the post-thaw quality of the specimen.
Management of Virtual Azoospermia
The primary goal of managing virtual azoospermia is to address any reversible factors that can potentially increase sperm counts and quality. Examples of these reversible factors include hormone abnormalities, varicoceles, lifestyle factors (such as use of hot tubs or saunas, smoking, and so on), and medications that might be detrimental to sperm production (see Sperm Boot Camp).
How Much Improvement Can Be Expected?
In general, if men start off in the virtual azoospermia range, success typically means getting sperm counts up to a point where there are plenty of sperm for IVF/ICSI. There are exceptions in which sperm counts may rise to the point of potential conception using IUI or even natural intercourse (examples would include men who had previously been on exogenous androgens, or perhaps who have had a very large varicocele treated). However, most men with only a few sperm to start will not be able to raise their counts up to a point at which IUI is possible.
If sperm counts improve to the point at which the IVF doctor and lab feel comfortable that enough sperm will be available to inject most or all of the eggs, then proceeding with IVF/ICSI is the next step. A double collection of sperm (two ejaculated specimens) on the day of egg retrieval can sometimes be useful in finding more fresh sperm. Ideally, the man would also have some backup frozen sperm in case his ejaculated sperm counts were lower on the day of egg retrieval. If no frozen backup specimens are available because counts were too low (or if the frozen specimens are of questionable quality), then the option of donor sperm as a backup should be considered, as should freezing any uninjected eggs.
What if sperm counts remain too low for IVF/ICSI?
If, after all reversible factors have been addressed, sperm counts are still considered too low for IVF/ICSI, then a fresh testicular biopsy can be considered. By going straight to the source of sperm production, enough live sperm can be found to inject all of the retrieved eggs approximately 50 percent of the time in men with virtual azoospermia (see “Azoospermia" section for more information on sperm extraction techniques). Ideally, this sperm retrieval would be timed with the day of the woman’s egg retrieval. The coordination of these two procedures can be challenging from a logistical standpoint, since the timing of the exact date when the woman’s eggs will be ready for retrieval is not known until a few days prior. Donor sperm backup or preparations for freezing eggs should be considered in these circumstances, in case enough sperm are not found in the testicular tissue. Providing a fresh ejaculated specimen if a fresh sperm extraction is coordinated with an IVF/ICSI cycle is a good idea in case higher numbers of sperm are present in the ejaculate that day. I have had one patient in which no sperm were found on testicular biopsy the day before egg retrieval, but enough sperm were present in an ejaculated specimen the next morning to inject all of the eggs.
If not enough sperm are found, then the couple can proceed with surgical sperm extraction techniques for Non-obstructive Azoospermia (NOA) as described in the "Azoospermia" section of this website. Other options would include adoption as well as donor sperm and donor embryo use.