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INTRAUTERINE INSEMINATION

SIR,-We have been following Lancet correspondence onintrauterine insemination (IUI), a treatment being used for a varietyof ill-defined conditions causing infertility. Dr Serhal and Dr Katz(Jan 3, p 52) do nothing to clear the confusion. An explanation fortheir apparent success with IUI should be sought, especially in viewof the pessimistic reports by others.l.2The key may be the cause of infertility being treated. Serhal and

Katz give little information on their diagnostic methods, but areasonable interpretation of their data is that in only 2 of the 23couples treated was the infertility due to sperm dysfunction, thesebeing the cases of negative post-coital tests (PCT) despite normalmucus and absence of antisperm antibodies, and treatment failed inthose cases. Inability of spermatozoa to penetrate normal cervicalmucus can be one of the most reliable indicators of spermdisorder.3,4 If Serhal and Katz’s 7 men with oligoasthenospermiaand 2 with antisperm antibodies did achieve positive PCTs,their infertility would seem to be essentially unexplained.Oligoasthenospermia is not a reliable index of sperm disorder anymore than normal seminal findings indicate normal spermfunction,s and antisperm antibodies may be irrelevant, especially ifpresent in blood rather than seminal plasma.

Unexplained infertility and primary disorder of cervical mucussecretion (implying normal sperm function in both cases) are thetwo conditions which we would expect to benefit from IUI-andindeed from intraperitoneal insemination (IPI) or gameteintrafallopian transfer (GIFT)--and they account for at least halfthe couples treated by Serhal and Katz. When Kerin et al6 reportedtheir encouraging results with IUI in the treatment of infertility dueto "poor quality semen" they were dealing with essentiallyunexplained infertility. The men had only mild to moderateoligoasthenoteratospermia. However, couples with "positivesperm-cervical mucus contact tests" (ie, sperm immobilisation)were excluded-in other words there was normal spenn-mucuspenetration, which indicates good sperm function3’ irrespective ofthe seminal findings.Our own working definition of sperm dysfunction depends on

reliable demonstration of failure of spermatozoa to penetrate andsurvive in normal preovulatory cervical mucus. Given repeatedlynegative post-coital tests8 we proceed to crossed penetration testingin vitro using normal donor mucus and semen samples as controls.We have now treated by IUI in 26 cycles 7 couples with such failureof sperm function and in whom the woman had normal menstrual

cycles, normal luteal progesterone levels and cervical mucus

secretion, and normal laparoscopic findings. The men had normalstandard seminal analysis, but 4 cases had antisperm antibodies inthe seminal plasma. Spermatozoa were prepared for inseminationby a layering technique and double washing of semen using Ham’sFlo medium. When antisperm antibodies were present the semensample was produced into 2 ml Ham’s FlO supplemented with 50%human serum albumin. Sperm density and proportions withprogressive motility and normal morphology were all improved bythis technique, and motile normal sperm density doubled.Insemination was performed when ovarian ultrasonographyshowed a follicle grown to at least 20 mm mean diameter and whencervical mucus secretion was at its peak8 which correlates well withthe time of ovulation in unstimulated cycles.9 In all cycles timing ofinsemination was confirmed retrospectively to have been done13-15 days before the next menstrual period, and the midlutealserum progesterone concentration was above 30 nmol/1. Highintrauterine insemination in 03 ml Ham’s Fio medium was donewith a Craft embryo transfer catheter (Rocket of London) in themanner described by Kerin.6 No pregnancies ensued.Our lack of success matches that in small series of mainly

unexplained infertility.l.2 Thomas et all described treating maleinfertility diagnosed simply by "abnormality in the semen analysis",but the PCT was negative in only 2 of their 10 couples. Irvine et apconfirmed sperm-fertilising ability in vitro by hamster eggpenetration. Although more than half of their couples had abnormalsperm-cervical mucus interaction (which they had previouslyshown to correlate with lack of fertilising ability) the degree ofabnormality defined by their method may not have been severe. Bycontrast, Yovich et ah° report IUI to have been moderately effectivein a larger series of mixed diagnoses, but they also used ovarian

stimulation in an unspecified number of cases. The specific benefitof superovulation and of its contribution to the apparent success ofIPI" and GIFT need to be assessed.We do not agree with Serhal and Katz’s view that IUI even when

appropriate should be tried only two or three times before

proceeding to IPI or GIFT. The pregnancy rates they achieved inthe first and second cycles of IUI treatment (5/23 and 1 / 10) were notsignificantly different and are likely to be maintained in subsequentcycles. More prolonged experience is needed, especially controlledstudies. We need more diagnostic precision, particularly in thedefinition of male infertility due to sperm dysfunction. We need toknow what we are treating in the first place. When spermatozoa areineffectual there seems little to be gained by simply delivering themcloser to the egg. - - om

Department of Obstetrics and Gynaecology,University of Bristol,Bristol Maternity Hospital,Bristol BS2 8EG

P.G. WARDLE

EILEEN MCLAUGHLINJENNIFER A. SYKESM. G. R. HULL

1. Thomas EJ, McTighe L, King H, Lenton EA, Harper R, Cooke ID Failure of highintrauterine insemination of husband’s semen. Lancet 1986; ii. 693-94.

2. Irvine DS, Aitken RJ, Lees MM, Reid C. Failure of high intrauterine insemination ofhusband’s semen. Lancet 1986; ii: 972-73.

3. Wardle PG, Mitchell JD, McLaughlin EA, Ray BD, McDermott A, Hull MGR.Endometriosis and ovulatory disorder: Reduced fertilisation in-vitro comparedwith tubal and unexplained infertility. Lancet 1985; ii: 236-39

4. Schats R, Aitken RJ, Templeton AA, Djahanbakhch O The role of mucus-sperminteraction in infertility of unknown aetiology. Br J Obstet Gynaecol 1984, 91:371-76.

5. Aitken RJ, Best FSM, Richardson DW, Djahanbakhch O, Lees MM An analysis ofsperm function in cases of unexplained infertility: Conventional criteria, movementcharacteristics and fertilizing capacity. Fertil Steril 1982; 38: 212-21.

6. Kerin JFP, Kirby C, Peek J, et al. Improved conception rate after intrauterineinsemination of washed spermatozoa from men with poor quality semen. Lancet1984; i: 533-35.

7. Hull MGR, Glazener CMA, Wardle PG, McLaughlin EA, Sykes JA. Male infertilitysperm penetration of mucus related to natural and in-vitro fertility. In Advances infertility and sterility. Lancaster: Parthenon Press (in press).

8. Hull MGR, Savage PE, Bromham DR. The prognostic value of the post-coital test aprospective study based in time-specific conception rates. Br J Obstet Gynaecol1982; 89: 299-305.

9. Depares J, Ryder REJ, Walker SM, Scanlon MF, Norman CM. Ovarian

ultrasonography highlights precision of symptoms of ovulation as markers ofovulation. Br Med J 1986, 292: 1562.

10. Yovich JL, Matson PL. Pregnancy rates after high intrauterine insemination ofhusband’s spermatozoa or gameta intrafallopian transfer. Lancet 1986; ii: 1287

11. Forrler A, Dellenbach P, Nisand I, et al. Direct intraperitoneal insemination inunexplained and cervical infertility. Lancet 1986, i. 916-17

PREDNISOLONE PHARMACOKINETICS ANDSTEROID PSYCHOSIS

SjR,—Glynne-Jones and colleagues (Dec 13, p 1404) imply thatabnormal peak concentrations of prednisolone cause steroid

psychosis and that enteric-coated prednisolone avoids the risk ofpsychosis by achieving delayed and lower peak steroid levels. Thereis an assumption, in the dose-for-dose substitution of enteric coatedfor plain tablets, that the two preparations are therapeuticallyidentical. This assumption is unjustified. Most studies of

bioavailability have revealed greater between-patient variability ofprednisone absorption with enteric-coated preparations. Thereference’ cited by Glynne-Jones et al refers to a shellac-coatedpreparation which was withdrawn for precisely this reason, andalthough the newer, cellulose-acetate-phthalate preparation showsbioavailability similar to that of plain prednisolone (and a delayedpeak absorption) when given in doses of 20 mg to healthyvolunteers a clinical study in renal transplant recipients revealedvery erratic absorption of larger doses which seemed to be not onlydelayed but also reduced by meals.3These studies suggest that substitution of enteric-coated

prednisolone for plain or soluble formulations may reduce the totaldose received by the patient and so lessen the therapeutic effectThis unintended dose reduction may have been responsible for thepattern of responses observed by Glynne-Jones et al.

Home Dialysis Office,Royal Victoria Infirmary.Newcastle on Tyne NE1 4LP

C. R. V. TOMSONM. C. VENNING

1. Wilson CG, May CS, Paterson JW. Plasma prednisolone levels in man followingadministration m plain and enteric-coated forms Br J Clin Pharmacol 1977, 4:351-55.

2. Lee DAH, Taylor GM, Walker JG, James VHT The effect of food and tableformulation on plasma prednisolone levels following administration of enteric-coated tablets Br J Clin Pharmacol 1979; 7: 523-28