Where there are identifiable anatomical defects of sperm transport, anatomical reconstruction may be done.
Assisted reproductive techniques include:
The cervix, with ideal mucus, acts as a reservoir for sperm. Only about 10 per cent of sperm in the ejaculate will reach the uterus. Penetration of cervical mucus depends on vigorous sperm motility. Cervical mucus filters out morphologically abnormal sperm or those coated with antisperm antibodies.
Table Infertility investigation – WHO values for a normal semen analysis.
|Appearance||Homogeneous, grey and opalescent|
|Liquefaction time||Within 60min at room temperature|
|Concentration||>20 million per ml|
|Motility||>50 per cent progressive motility|
|Morphology||>30 per cent normal forms|
|White blood cells||<1 million per ml|
|Viability||75 per cent or more viable|
|Immunobead test||<20 per cent spermatozoa with adherent particles|
Table Clinical categorisation of infertile men.
|Primary testicular failure|
|Androgen receptor defects|
|Postinflammatory mumps orchiditis|
|Undescended testes (past or present)|
|Past cytotoxic or X-ray therapy|
|Total teratospermia (absent acrosomes, decapitate sperm)|
|Zero sperm motility (immotile cilia syndrome)|
|Specific defects of sperm-oocyte interaction (e.g. disordered zona pellucida induced acrosome reaction)|
|Genital tract obstruction|
|Reversible toxin exposure – illness|
|Subfertility currently without proven effective treatment|
|Idiopathic oligospermia, asthenozoospermia, teratozoospermia or combinations|
|Associated conditions: varicocele, genital tract inflammation, adverse lifestyle factors|
If sperm concentration is low, or if many of the sperm are poorly motile, morphologically abnormal or coated with antibody, too few may penetrate the cervix and reach the fallopian tubes. Fertilisation is unlikely to occur.
■ Sperm suitable for Intrauterine insemination can be separated by swim-up percoll density gradient into culture medium to obtain a specimen enriched in motile normal sperm.
■ Washing the sperm reduces the sperm count to 10 per cent. At least 1 million are needed for successful fertilisation.
■ The sperm is free of leukocytes.
■ The chance of conception is enhanced by superovulating the partner and increasing the number of eggs with accurate timing of insemination.
Table Effect of drugs on fertility.
|Drug||Effect on fertility|
|Sulphasalazine (when used to treat inflammatory bowel disease)||Decreases sperm concentration and motility and increases abnormal morphology|
|Nitrofurantoin||Spermatogenic arrest and decreased sperm counts at high dosage|
|Tetracyclines||Chlortetracycline and minocycline, in particular, bind to spermatozoa and interfere with sperm motility|
|Cimetidine||As a weak antiandrogen, it has been associated with seminal abnormalities as well as gynaecomastia and impotence|
|Ketoconazole||Single oral doses reduce serum testosterone concentrations although the clinical importance of this is unknown. Gynaecomastia, loss of libido and impotence have also been reported|
|Colchicine, allopurinol||Associated with defects of fertilisation capacity of sperm as demonstrated by abnormal sperm penetration tests|
|a-drenoreceptor blocking agents (e.g. methyldopa, clonidine, terazosin, phentolamine, phenoxybenzamine), tricyclic antidepressants (e.g. imipramine, amitryptyline, trimipramine), monoamine oxidase inhibitors (e.g. phenelzine, tranylcypromine), phenothiazines (e.g.chlorpromazine, thioridazine)||Ejaculatory dysfunction|
|Chemotherapeutic agents, especially alkylating agents||Affect spermatogenesis through a direct effect on germinal epithelium.May also cause transient chromosomal aneuploidies in sperm|
|Cannabis||follicle-stimulating hormone and luteinising hormone secretion is decreased leading to defective testicular function and spermatogenesis.Libido may also be decreased|
|Cocaine||Decreases sperm concentration and motility. Increases proportion of abnormal forms|
|Anabolic steroids||Decreased secretion of follicle-stimulating hormone and luteinising hormone via feedback inhibition of the hypothalamus and pituitary gland, which can lead tohypogonadotrophic hypogonadism. Sperm concentration, motility and normally formed sperm are all reduced but are reversible after stopping steroids. Azoospermia, gynaecomastia and reduced libido have also been reported|
|Non-steroidal anti-inflammatory drugs||Associated with an increasedincidence of luteinised unruptured ovarian follicles|
|Chemotherapeutic agents, especially alkylating agents||Ovarian failure. Degree of reversibility dependent on drugs used and age of woman|
|Cannabis||Oligomenorrhoea and anovulation|
■ Intrauterine insemination is suitable for couples with mild to moderately impaired semen analysis. It is likely to be less successful than conventional In vitro fertilisation but cheaper per cycle.
■ Where sperm dysfunction has been demonstrated, Intracytoplasmic sperm injection is the treatment of choice because success rates from In vitro fertilisation are decreased due to a decreased fertilisation rate and the chances of success by Intrauterine insemination are unknown.
Intracytoplasmic sperm injection
Intracytoplasmic sperm injection involves the injection of a single spermatozoon through the zona pellucida directly into the oocyte. Intracytoplasmic sperm injection is the procedure of choice when epididymal or testicular sperm is obtained surgically from patients with an obstructive or non-obstructive azoospermia, because fertility rates using sperm from the testis are poor in In vitro fertilisation.
Table Effects of occupational factors on fertility.
|Occupation/exposure||Effect on fertility|
|Agricultural chemicals especially pesticides, e.g. dibromochloropropane (DBCP)||Oligozoospermia and azoospermia, some of which is reversible|
|X-ray exposure||High exposure may lead to reduced sperm count|
|Ethylene glycol ethers and their acetates, used in preparations containing solvents, especially paint products||May decrease sperm count but fertility not necessarily affected|
|Heavy metal exposure (e.g. mercury, arsenic, cadmium, lead, manganese). This can occur during the processes of smelting and welding, and in chemical factories||Lead, in particular, seems to be associated with decreased fertility in couples whilst the male partner is exposed. However, confounding factors such as concurrent exposure to heat need to be taken into account|
|VDU use||No effect detected|
|Anaesthetic gases||No effect proven for either male or female exposure|
|Environmental pollutants, e.g. polychlorinated biphenyls (PCBs) found in insecticides, fungicides and herbicides||Multiple exposure makes toxic effects of one individual compound difficult to evaluate. Possible detrimental effect on oocyte recovery during In vitro fertilisation in women with high follicular fluid concentrations of PCGs|
Table Patency rates and pregnancy rate (n = 1469) in microsurgical vasectomy reversal procedures. Microsurgical epididymal sperm aspiration and Intracytoplasmic sperm injection results in a 29% delivery rate. Epididymal sperm aspiration and Intracytoplasmic sperm injection should be reserved for failed surgery or causes not amenable to surgical reconstruction.
|Interval after vasectomy (years)||Patency rate (%)||Pregnancy rate (%)|
Table Other causes of obstructive azoospermia. Obstructive lesions of the seminal tract should be suspected in azoospermia or severe oligospermia with normal-sized testes (> 15-20ml volume).
|Conditions||Patency rate (%)||Pregnancy rate (%)|
|Epididymovasostomy (postinfective) blocks in the cordal part of the epididymis||52||38|
|Obstruction in the capital part of the epididymis (not due to an infective aetiology)||12||3|
|Postinfective obstruction in the vas (corrected by total anatomical reconstruction)||73||27|
A single motile spermatozoon is immobilised and aspirated, tail first, into the injection pipette. The oocyte is fixed with a holding pipette with the polar body situated at the 6 o’clock position. The injection pipette is put through the zona pellucida and the oolemma into the cytoplasm at the 3 o’clock position and the sperm is delivered with the smallest amount of medium. With the oocyte orientated in this way there is minimal risk from the injection pipette damaging the metaphase plate.
Oocytes are considered to be normally fertilised when two pro-nuclei are visible. Embryo cleavage of normally fertilised oocytes is assessed 24 hours after further in vitro culture. They are graded 1 (excellent, type A embryos with no anucleate fragments), 2 (good quality, type В embryos with between 1 and 20 per cent of the volume filled with anucleate fragments) and 3 (fair quality, type С embryos with between 21 and 50 per cent of the volume filled with anucleate fragments).
Delivery rates vary from 22 to 30 per cent per Intracytoplasmic sperm injection treatment cycle.
Complications for children born after Intracytoplasmic sperm injection
There is a statistically significant increase in sex chromosome aberrations compared with data in the literature on a normal neonatal population (about twice the rate of the non-Intracytoplasmic sperm injection population). However, it is clear that this increased incidence is related to the increased risk of chromosomal aberrations in the parents and the concomitant sperm abnormalities as a result of these. There is no increased risk with vasectomy reversal, cryptorchidism, major deformity of the vas, or obstructive azoospermia. There is no statistical difference in outcome measured in terms of prematurity, low birth weight, very low birth weight or loss of pregnancy.
Risk advice prior to treatment for infertility
Ovulation induction has an associated risk of ovarian hyperstimulation which can be a life-threatening situation if the woman gets pregnant. Therefore she must be carefully counselled about the risks and the ovulatory dose of human chorionic gonadotrophin withheld or the eggs retrieved, fertilised and embryos frozen to avoid pregnancy associated with ovarian hyperstimulation. The real risk of assisted reproductive techniques is the increased risk of multiple pregnancy with the associated risks of preterm labour and long-term complications. The perinatal mortality rate in 1995 of twins was 40 per 1000, in stillbirths 65.1 per 1000, compared with 8 in 1000 for singletons. The incidence of cerebral palsy in triplets is 47 times more than that of a singleton. The rate for cerebral palsy in twins is approximately 7 per 1000 births, and for triplets 27 in 1000 compared with 1.5 in 1000 for singletons.
Recently the risk of ovarian cancer associated with the use of fertility drugs has been reported.