Clinical review 100: Evaluation and treatment of the infertile couple

Abstract

Infertility by itself does not threaten physical health but has a strong impact on the psychological and social well-being of couples. In the last two decades, progress in caring for the infertile couple, in particular progress in the field of assisted reproduction and micromanipulation, has provided significant hope for many couples for whom hope could not have been offered in the past. This is especially true for bilateral tubal disease and for male factor infertility, as nearly all couples with male factor infertility can now undergo either one (or more) IVF or ICSI attempt(s). For couples with other causes of infertility, however, the differences in pregnancy rates often do not reach statistical significance. We must also remember that the total cost incurred for successful delivery for couples with a better chance of successful IVF (i.e. those with tubal disease) increases from approximately $55,000 in American dollars for the first cycle to $73,000 by the sixth cycle. Because of these high costs, many insurers in the United States and many public health systems in Europe do not cover or only partially cover these procedures. Consequently, the availability of IVF and related therapies frequently depends on the couple's ability to pay. Therefore, after having established the correct diagnosis, appropriate treatment should be counseled to the infertile couple keeping in mind the following points: 1) in subfertile couples expectant management should be reasonably counselled if the age of the woman is less than 30 yr and the duration of infertility is less than 36 months, even if oligozoospermia is present; 2) superovulation and timed intercourse seems also to be a reasonable approach in couples with anovulatory, mild/moderate endometriosis, and unexplained infertility; 3) in unexplained infertility, ovarian stimulation (with clomiphene or gonadotropin) and IUI seem to offer some advantage over ovarian stimulation and timed intercourse; 4) IVF can be a firstline approach in tubal sterility and when IUI or IPI cannot be performed because the number of motile sperm is insufficient, but is usually also the final treatment attempt when other methods have failed. The outcome of IVF is negatively influenced mainly by the woman's age; however, the number of deliveries is also generally lower in couples with male factor; 5) ICSI is a further option, which should be limited to couples: a) with very poor semen parameters; b) previous failed fertilization; c) presence of obstructive or nonobstructive azoospermia in which ICSI is combined with sperm extraction from the epididymis or the testis; 6) international register studies demonstrate that the risk of malformation after conventional IVF is not increased; 7) some reports suggest that incidence of congenital major and minor malformations is not increased in children born after ICSI. However, the rate of sex chromosome anomalies in ICSI fetuses has been reported to be approximately 1% in 585 prenatal diagnoses, a frequency increased by a factor of 4 if compared with naturally conceived live-born babies. ICSI bypasses the physiological selection of spermatozoa that occurs at the level of the testis and epididymis, and in the female reproductive tract as well as at the sperm-oocyte interface. As genetic abnormalities are present in a significant percentage of infertile males with impaired spermatogenesis, karyotyping and analysis of the Y chromosome for microdeletions should be carried out in all potential ICSI fathers. Screening for cystic fibrosis gene mutations should also be performed in azoospermia caused by congenital absence of the vas deferens and seminal vesicles. Appropriate genetic counseling should be made available to all ICSI couples whenever a gene or chromosomal anomaly has been identified. With most ARTs the average delivery rate per cycle is approximately 15% and the cumulative delivery rate after several cycles is about 50%. (ABSTRACT TRUNCATED)