Intrauterine insemination of washed husband’s spermatozoa: a controlled study

FERTILITY AND STERILITY

Vol. 51, No.1, January 1989

Copyright " 1989 The American Fertility Society

Printed in U.S.A.

Intrauterine insemination of washed husband's spermatozoa: a controlled study

Egbert R. te Velde, M.D.* Roelof J. van Kooy, Ph.D. Jolanda J. H. Waterreus, M.D. Division of Reproductive Medicine, Department of Obstetrics and Gynecology, University Hospital, Utrecht, The Netherlands

Although intrauterine insemination (lUI) with husband's semen has been practiced extensively and for many years, little controlled evidence is available to show a beneficial effect. 1 We performed lUI with washed husband's spermatozoa in couples with clear evidence of impaired sperm-mucus interaction and in couples in whom male subfertility was the only abnormality found. The aim of the study is to establish whether or not lUI in such couples leads to more pregnancies than normal intercourse during noninduced, ovulatory cycles. MATERIALS AND METHODS Patients

Fifty-seven couples with a long-standing history of infertility (mean, 5.2 years; range, 3 to 12 years) took part in the study. In most of the couples (88%), there was a primary infertility. All women were considered to have normal ovulatory cycles because of a biphasic pattern of the temperature curve and normal progesterone levels during the luteal phase. On the hysterosalpingogram and at laparoscopy, no abnormalities were seen that could explain the infertility. Semen qualities were assessed on at least three occasions. The specimen showing the best results was taken into account. This specimen had to conReceived March 24, 1988; revised and accepted September 16,1988. :Reprint requests: Egbert R. te Velde, M.D., Department of Obstetrics and Gynecology, University Hospital, Catharijnesingel101, 3511 Utrecht, The Netherlands. 182

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tain at least 10 X 106 motile spermatozoa (volume X concentration X% motility). Two main indications for lUI were observed: male subfertility, and impairment of sperm-mucus interaction. Male Subfertility

For a couple to be entered into this group (n 30), the following conditions had to be met: (1) One or a combination of the following sperm qualities was present: <20 X 106 sperm per ml (oligospermia), a motility of 40% or less (asthenospermia) and <50% morphologically normal spermatozoa (teratospermia); (2) Either the postcoital test (PCT) showed a positive result (the presence of motile spermatozoa) and the sperm-mucus penetration test (SPM) 2 a good result (most couples), or the cervical mucus had to be of good quality (Insler score3 of 11 or more) on at least one occasion. The poor results of PCTs and SPMs in the latter were thought to be due to suboptimal sperm qualities. (3) There was no evidence of sperm antibodies, as measured by the direct mixed agglutination reaction.4 A summary of the semen qualities of the Male Subfertility group is given in Table 1. =

Impairment of Sperm-Mucus Interaction

Couples were entered into this group (n = 27) when the results ofthe repeatedly (3 times or more) performed PCT were suboptimal (immotile spermatozoa) or negative, and the result of the SPM was poor or negative. These results could not be explained by suboptimal timing of the test. Three subgroups <;an be distinguished: Fertility and Sterility

Table 1

Semen Qualities of the Male Subfertility Group Mean and range Quality

Oligospermia Asthenospermia Teratospermia Oligoasthenospermia Oligoteratospermia Asthenoteratospermia Oligoasthenoteratospermia Total

No. of patients 6 6

Motility

Morphology

xw•

%

%

9 (5-14) 32 (20-40) 26 (24-28)

2

7 3 2 4 30

1. Immunologic Subgroup (n = 8). In these patients the direct mixed agglutination reaction on spermatozoa4 was strongly positive for gamma G immunoglobulin (IgG; 90% or more) and positive for gamma A immunoglobulin (lgA), reflecting the presence of antisperm antibodies. With the crossed spermcervical mucus contact test, 5 the presence of antisperm antibodies was confirmed in the man and excluded in the woman. 2. Explained Cervical Hostility Subgroup (n = 15). In 3 couples, pH measurements of the endocervical mucus always showed a value of 6.3 or less. 6 In the remaining 12 couples, the quality ofthe cervical mucus was always moderate or poor (Insler score <6). In 11 of these 15 couples, the lower margin of normality for one or two of the semen qualities, described above, was not reached. 3. Unexplained Cervical Hostility Subgroup (n = 4). In four couples with normal sperm and good mucus qualities, the repeatedly poor results of the PCTs and SPMs remained unexplained. Study Design

No ovulation induction methods were used. In each couple, insemination cycles were alternated with cycles during which normal intercourse took place. Both types of cycles were monitored for luteinizing hormone (LH), using a rapid radioimmunoassay. Daily plasma determinations started from the tenth day of the cycle, until a clear rise of LH levels could be detected. In the insemination cycle, lUI with a preparation of washed spermatozoa was scheduled for the following day. The couple was asked to abstain from intercourse until 3 days after the .time of insemination. During the intercourse cycles, intercourse was advised on the evening of the day of the LH rise and on the following day. Vol. 51, No.1, January 1989

Concentration

16 (10-19) 7 (3-12) 12 (8-17)

34 (20-40) 25 (20-30) 32 (20-40)

41 (38-45) 36 (35-37) 39 (31-48)

The intercourse pattern was not further influenced. Each couple was offered six insemination and six intercourse cycles. The type of cycle on which the couple started was allocated randomly. At the time of data collection, six couples had only completed one cycle: three because a pregnancy had occurred, and three because the couple had recently entered into the program. The results were analyzed by comparing the pregnancy rates of the insemination and intercourse cycles. The chisquare test, with Yates' correction for continuity, was used. Semen Preparation and Insemination

For the preparation of the spermatozoa, Earl's medium supplemented with 8% inactivated human serum was used. The male partner was asked to produce semen in two fractions (split ejaculate). The best fraction of the split ejaculate was diluted 1:1 with medium after liquefaction had taken place. When antisperm antibodies were present, the man was asked to ejaculate directly into a beaker containing 10 ml medium. That mixture was homogenized and centrifuged as soon as possible, to ensure a minimal contact time between spermatozoa and seminal plasma. The diluted semen was placed onto 70% percol (Pharmacia, Uppsala, Sweden) and centrifuged 15 minutes at 300 X g. The pellet containing the spermatozoa was washed twice with medium by resuspension and centrifugation for 5 minutes at 200 X g. Immediately before insemination, the spermatozoa were taken up in maximally 0.5 ml medium, drawn into the tip of a polyethylene insemination catheter, and subsequently inseminated into the uterine cavity. RESULTS

The results of the Male Subfertility group are given in Tabl~ 2 (left side). There was no difference te Velde et al.

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Table 2 Results of Intrauterine Insemination in Couples with Male Subfertility and in Couples with Impairment of Sperm-Mucus Interaction Male subfertility

Impairment of sperm-mucus interaction

Cycles Patients Total number Pregnancy occurred in: %pregnancy Significance

30

5 17

Insemination

Cycles Intercourse 90 2

112 3

2.2

2.7 NS"

Patients

Insemination

Intercourse

27 13 48

82

61

13 16

0 0 <0.01

• NS, not significant.

in the pregnancy rates of the insemination and intercourse cycles. The mean duration of infertility was 5.8 years (range, 3 to 10 years) in the couples becoming pregnant and 5.7 years (range, 3 to 10 years) in the couples in whom no pregnancy occurred. Of the five patients who became pregnant, fertilization occurred in the first, the second, the fifth, the ninth, and the 11th cycle. In Table 2 (right side), the results are given for the Impairment of Sperm-Mucus Interaction group. The difference between pregnancy rates of the insemination and intercourse cycles is statistically highly significant. All pregnancies occurred during insemination cycles. The mean duration of infertility of the couples becoming pregnant and not becoming pregnant was 4 (range, 3 to 6) and 5.1 (range, 3 to 12) years, respectively. In contrast to the Male Sub fertility group, in most couples, fertilization occurred during one of the first attempts. The number of insemination cycles of the couples who became pregnant was one (n = 5), two (n = 7), and six (n = 1). In the Immunologic (n = 8) and the Cervical Hostility (n = 19) subgroups, three (37%) and ten (52%) pregnancies were established, respectively. In the 11 couples of the Explained Cervical Hostility subgroup, where subnormal semen qualities were found, five pregnancies (45%) occurred. DISCUSSION

The results of this study indicate that, in couples in whom male subfertility is the only detectable abnormality, LH-timed lUI is not of substantial advantage in comparison with LH-timed intercourse. In contrast, lUI appeared to be successful in the . Impairment of Sperm-Mucus Interaction group. Twelve of the 13 pregnancies of this group occurred during the first or second insemination cycle. Con184

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sidering the long duration of infertility, this finding further points to the therapeutic potential of lUI in such patients. When assessing infertility treatment, it is essential to take account of treatment-independent pregnancy rates before claiming a therapeutic effect. Therefore, controlled randomized trials are mandatory to accept the effect of any infertility treatment. 7 To our knowledge, only one study evaluating lUI versus normal intercourse in noninduced ovulatory cycles, was cycle-controlled and randomized like ours. 8 In contrast with our study, however, Kerin et al. came to the conclusion that improved conception rates in male subfertility do occur after lUI. Although patients with a positive sperm-cervical-mucus contact test were excluded in this study, neither the cervical mucus qualities nor the results of postcoital testing were taken into account. In our experience, cervical hostility and moderate male subfertility are not a rare combination. We found a pregnancy rate of 45% in such couples, which was about the same as in the whole Impairment of Sperm-Mucus Interaction group. If these 11 couples would have been included in the male subfertility group, the pregnancy rates would have been clearly in favor of intrauterine in semination for male subfertility. These considerations also raise the question of whether the poor results of lUI in the Male Subfertility group are rather due to other, but unknown, causes of infertility, than by the subnormal semen qualities per se. Without any information on the sperm-mucus interaction and cervical mucus qualities, the claim of Kerin et al. that lUI in male subfertility has a therapeutic effect is premature. Because the presence of antisperm antibodies on most spermatozoa was the obvious cause of the poor results of the PCTs and SPMs, we included couples in whom immunologic male infertility was Fertility and Sterility

convincingly present in the Impairment of SpermMucus Interaction group. The results of the three successful couples (duration of infertility: 4, 5, and 9 years) indicate that, in the presence of antisperm antibodies in the male partner, bypassing the cervix with lUI may solve the problem. In conclusion, the main objective of this study was to determine whether lUI of washed husband's spermatozoa during spontanous ovulatory cycles leads to more pregnancies than normal intercourse. The results indicate that, in couples with subnormal semen but optimal cervical mucus qualities, lUI is of no advantage to normal intercourse. In contrast, when an obvious impairment of the sperm-mucus interaction is diagnosed, lUI is a relatively successful treatment, also in the presence of subnormal semen qualities. No answer can be given on the question of whether LH monitoring, allowing for intercourse or insemination during the most fertile period, has a positive effect on conception rates. Moreover, whether or not lUI during stimulated cycles will improve conception rates can be decided only after a prospective, controlled trial.

lUI was scheduled or intercourse advised for the following day. In the male subfertility group no difference between the pregnancy rates of insemination and intercourse cycles was present. In the group with impairment of sperm-mucus interaction, the pregnancy rate of the insemination cycles was 16%, whereas no pregnancies occurred during intercourse cycles. Acknowledgements. The authors wish to thank the technical staff of the laboratory for fertility investigation for their enthu · siastic assistance and the registrars of the department of Gy· naecology and Obstetrics for performing inseminations seven days a week.

REFERENCES 1. Allen NC, Herbert CM III, Maxson WS, Rogers BJ, Dia·

2. 3. 4.

SUMMARY

We performed intrauterine insemination with washed husband's spermatozoa in 27 couples with clear evidence of impaired sperm mucus interaction due to cervical hostility or immunologic male subfertility and in 30 couples with subnormal semen, but optimal cervical mucus qualities. In each couple insemination cycles were alternated with cycles during which normal intercourse took place. Both types of cycles were monitored for LH. When a clear rise of LH levels could be detected, either

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5. 6.

7. 8.

mond MP, Wentz AC: Intrauterine insemination: a critical review. Fertil Steril44:569, 1985 Kremer J: A simple sperm penetration test. Int J FertillO: 209, 1965 Insler V, Herzel M, Eichenbrenner I, Serr DM, Lunenfeld B: The cervical score. Int J Obstet Gynecol10:223, 1972 Jager S, Kremer J, Kuiken J, van Slochteren-Draaisma T: Immunoglobulin class of antispermatozoal antibodies from infertile men and inhibition of in vitro sperm penetration into cervical mucus. Int J Androl3:1, 1980 Kremer J, Jager S: The. sperm-cervical mucus contact test: a preliminary report. Fertil Steril 27:335, 1976 Kroeks MVAM, Kremer J: The pH in the lower third of the genital tract. In The Uterine Cervix in Reproduction, Edited by V Insler, G Bettendorf, Stuttgart, Georg Thieme Publishers, 1977, p 109 Glass RH, Ericsson RJ: Spontaneous cure of male infertility. Fertil Steril31:305, 1979 Kerin JFP, Peek J, Warnes GM, Kirby C, Jeffry R, Matthews CD: Improved conception rate after intrauterine insemination of washed spermatozoa. Lancet 2:533, 1984

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