The Role of Artificial Reproductive Technology (ART)
in the Treatment of Male Factor Infertility

Anne Borkowski, MD, Board Certified Reproductive Endocrinologist,
North Shore Fertility, Skokie, ILL

Infertility affects 1 in 12 couples. Male factor infertility is a component of approximately 40% of these cases. Less that 10% of male factor infertility can be treated successfully with medical or surgical modalities. The best therapies for over 90% of male infertility patients are controlled ovarian hyperstimulation with intrauterine inseminations or in vitro fertilization.

The problem for some couples is one of numbers. A normal ejaculate contains over 40 million sperm. Of this large number, only a few hundred will reach the fallopian tubes. If there is a decrease in the initial number of normal sperm, there may be too few sperm reaching the fallopian tubes to make fertilization likely. The purpose of intrauterine inseminations (IUIs) is to achieve a higher concentration of sperm in the fallopian tubes.

Placing sperm into the uterine cavity involves coordination of the therapy with that of the female in one of three ways: natural cycles, clomiphene citrate induced cycles, or gonadotropin stimulated cycles. There is considerable controversy over the use of unstimulated cycles with IUIs for male factor infertility. Overall pregnancy rates are low (approx. 4% per cycle). Most pregnancies occur within the first three to four cycles; therefore the number of unstimulated IUI cycles should be limited.

The use of Clomid with IUIs is based on the assumption that the release of more oocytes leads to a greater chance for pregnancy. However, pregnancy rates with clomiphene remain low (approx. 5% per cycle)), and occur within the first 3 cycles. Gonadotropin stimulation with IUIs does offer an increased pregnancy rate over other protocols (approx. 9%). Still, pregnancies tend to occur within 3 cycles. Since pregnancy rates are much higher with IVF combined with intracytoplasmic sperm injection (ICSI) for male factor infertility, couples often resort to this as a first line therapy. ICSI has revolutionized the treatment of male factor infertility so much that when doing IVF with ICSI, female factors and not male factors determine outcome. Routine fertilization rates of more than 66% of oocytes are obtained with ICSI using sperm from men with triple sperm defects (i.e. count, motility, morphology). Clinical pregnancy rates are greater than 28% per cycle. To date there is no increased incidence of congenital malformations in children born as a result of ICSI. However, there are concerns that because some causes of male infertility are unexplained and may be genetic, male offspring might have reproductive problems as adults.

Since the introduction of ICSI, treatment of most men with azoospermia is now possible, even if the azoospermia is caused by testicular failure. Before initiating treatment it is important to determine whether the lack of sperm in the ejaculate is from retrograde ejaculation, an obstructive process, or a non-obstructive process. Evaluation of the post ejaculate urine is necessary to diagnose retrograde ejaculation. Sperm may be isolated from urine or catheterized from the bladder and used for IUI or IVF. Men with obstructive azoospermia typically have normal volume testis with bilaterally indurated epididmii or absent vas deferens, which is frequently found in men who carry the cystic fibrosis gene mutation. Men with non-obstructive azoospermia usually have small, soft testis and elevated FSH levels.

The two procedures that are most commonly used to retrieve sperm from azoospermic men are the testicular sperm aspiration (TESA) and the midepididymal sperm aspiration (MESA) procedures. TESA is an open testicular biopsy during which about 500 mgs of testicular tissue is excised using scissors. MESA involves puncturing individual epididymal tubules and aspiring the fluid. During both procedures specimens are examined in the operating room to insure an adequate number of sperm are retrieved.

In the past, sperm aspiration procedures were performed the same day as the oocyte aspiration. thus allowing the use of fresh sperm for ICSI. However, cryopreservation of epididymal and testicular sperm allows for temporal separation of sperm retrieval procedures from oocyte aspiration. It allows for multiple ICSI cycles without the need for additional sperm retrieval procedures. It also insures a couple that they will not be cancelled the day of the oocyte aspiration due to inability to obtain sperm from TESA/MESA.

Cryopreservation is known to impair motility and decrease the fertilization rate by detrimental effects on the acrosomal structure and function. Fortunately, ICSI obviates the requirement for sperm motility and acrosome function. Therefore, it is not surprising that several recent studies have shown fertilization rates using frozen-thawed sperm combined with ICSI are as high as those with freshly harvested sperm.

All of the aforementioned techniques have significantly increased the demand for male infertility services. Sperm retrieval from men with azoospermia is now possible with excellent pregnancy rates when combined with ICSI. These advancements allow for fertility treatment where the only options several years ago were donor sperm or adoption.

 

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