Insemination of sperm can be into the cervix or into the uterine cavity. Intracervical insemination is most often performed if the couple’s only apparent problem with fertility is the inability to complete intercourse. Otherwise, this is a technique with limited proven utility. The primary indication for intrauterine insemination without the addition of controlled ovarian hyperstimulation is an abnormal postcoital test or a subtle male factor. Intrauterine insemination requires that the sperm is “washed” free of the semen since semen
- contains molecules (called prostaglandins) that cause painful contractions of the uterus if placed into the uterine cavity,
- may contain bacteria, and
- may have oxygen reactive species of molecules that could interfere with fertilization.
Techniques to separate sperm from semen can partially determine the amount and quality of sperm inseminated. Many infertility specialists have suggested that 1 million motile sperm following the sperm separation procedure is the minimum amount of sperm associated with a reasonable chance of pregnancy success at intrauterine insemination. The basis of this suggestion is not clear from a review of the literature, however, my own personal experience is in general agreement.
Sperm washing techniques include:
(1) Simple washing:
following centrifugation, resuspension of the sperm pellet into an inert buffered media. This technique does not eliminate dead sperm or debris from the resuspended washed sperm
following centrifugation an inert buffered media is layered over the unagitated sperm pellet and some of the motile sperm will swim toward the surface. Generally it takes 30-60 minutes for the sperm to swim out of the pellet and then the media near the surface with the motile sperm is collected. There will be a lower sperm count following this procedure due to the elimination of dead sperm but the quality of the motile sperm may be improved
(3) Gradient differential centrifugation:
inert particles are suspended in an inert buffered media at differing densities (concentrations) and layered so that following centrifugation the motile sperm fraction of the semen will be found isolated within a certain layer (density). Percoll (silicone particles with polyvinyl pyrrolidine links) was widely used for this indication until removed from this market in 1996 (potentially hazardous endotoxin levels were identified). Research has suggested that the recovery of motile sperm is better with Percoll than with the swimup technique, and that the harmful effects of oxygen reactive species of molecules is less significant with the Percoll technique as compared to swimup. Other particles are now available for differential centrifugation, one of the more common after 1999 being “Isolate.”
swimup into chemicals such as hyaluronidase or filtration through glass wool (which reportedly will adhere selectively to dead sperm) are occasionally used but not widely accepted at this time.
In sperm with decreased motility, chemical agents similar to caffeine have been used to enhance motility. These agents include pentoxyfylline which when applied to sperm will often improve motility considerably. The use of these agents has been significantly reduced over the past several years by concerns of possible embryotoxicity and concurrent advances in assisted fertilization techniques (eg., ICSI).
The criteria for the timing of inseminations should be clearly established. The goal is to perform the insemination around the time of ovulation. Ovulation occurs about 36 hours after the onset of the LH surge (signal from the brain to the ovaries to ovulate) during a natural cycle. Ovulation predictor kits detect LH in the urine (after metabolism and excretion into the urine) since LH in the urine reacts with the test kit material to change its color (to pink or blue). The detection of high levels of LH in the urine correlates with the occurrence (not the onset) of the LH surge in the blood. Generally, ovulation will then occur the day of or the day following the positive LH ovulation predictor kit result (exact timing of ovulation with these kits is not possible). On occasion, ovulation may occur 2 days after the kit’s detection of the LH surge. I normally recommend an IUI the day of or the day following a positive ovulation kit result.
The timing of ovulation may also be controlled more closely with serial ultrasound exams and “triggering” ovulation with medication. HCG and LH hormones share cellular receptors in the ovary so that an injection of hCG hormone simulates the LH surge to effectively initiate the cascade of events that lead to ovulation some 36 hours later.
With hCG triggered ovulation research suggests a higher pregnancy rate when 2 IUIs are performed with the initial procedure at 18 (12-24) hours and the second procedure at 42 (36-48) hours. It would be helpful to have more research information concerning the benefit of two versus one IUI per treatment cycle.