Human Reproduction vol.12 no.6 pp.1165–1170, 1997
Treatment of male infertility due to sperm surface
antibodies: IUI or IVF?
W.Ombelet1,3, H.Vandeput1, M.Janssen1, A.Cox1,
C.Vossen1, H.Pollet1, O.Steeno2 and E.Bosmans1
1Genk
Institute for Fertility Technology, St Jansziekenhuis,
Schiepse Bos 6, 3600 Genk, and 2Department of Internal Medicine
of the Catholic University of Leuven, Leuven, Belgium
3To
whom correspondence should be addressed
This prospectively designed study was aimed at comparing
the results of two different treatment protocols in 29
infertile couples with proven male immunological infertility,
i.e. a positive (>50%) mixed antiglobulin reaction (MAR)
test (IgG and/or IgA). In the first protocol (group I, n
J 14) couples were treated with ovarian stimulation/
intrauterine insemination (IUI), followed by in-vitro fertilization (IVF) if no pregnancy occurred after three IUI
cycles. In the second protocol (group II, n J 15), patients
were treated with IVF as a first choice procedure. The
decision to follow protocol 1 or 2 was made by the couples
after information about financial costs and expected success
rates (according to the literature) for both treatment
options. In group I, nine patients (64.3%) conceived after
a maximum of three IUI cycles whereas seven patients
(46.6%) of group II became pregnant during the first IVF
cycle. The take-home baby rate per started IUI or IVF
cycle was 27.3% (9/33) and 44.4% (16/36) respectively with
a take-home baby rate of 64.3% after three IUI cycles and
93.3% after three IVF attempts. To conclude, both IUI and
IVF yielded unexpectedly high pregnancy rates in this
selected group of patients with long-standing infertility due
to sperm surface (predominantly IgG) antibodies. Since
cost benefit analysis comparing superovulation IUI with
IVF may favour a course of four IUI cycles, we advocate
superovulation IUI as the first line therapy in male immunological infertility.
Key words: antisperm antibodies/intrauterine insemination/invitro fertilization/male infertility
Introduction
The clinical significance of antisperm antibodies (ASA) in
male infertility remains unclear (Ru¨mke, 1980; Husted and
Hjo¨rt, 1975; Barratt et al., 1992; Jarow and Sanzone, 1992)
and the importance of circulating ASA is probably low (Critser
et al., 1989; Eggert-Kruse et al., 1989; Marshburn and Kutteh,
1994). However, most studies demonstrate a clear association
between sperm surface antibodies and the fertility potential of
the male (Hjo¨rt and Hansen, 1983; Adeghe et al., 1988;
Hammitt et al., 1988; Matson et al., 1988; Acosta et al., 1994)
© European Society for Human Reproduction and Embryology
although Barratt et al. (1992) demonstrated a lack of correlation
between low (,10%) and moderate (,50%) ASA positive
binding cases and the probability of conception or the time to
conception.
ASA found in semen are usually immunoglobulins of the
IgG or IgA isotype that are directed to various sites of the
spermatozoa, i.e. head, midpiece, tail, or combinations thereof
(Peters and Coulam, 1992). IgGs in semen are mostly regarded
as transudates from the systemic circulation via the prostate
gland, whereas IgA is usually (60–90%) secretory in type,
suggesting intratesticular and/or epididymal synthesis (Adeghe,
1992). The binding of these antibodies can be directed toward
carbohydrate or peptide moieties of sperm antigens, but the
binding can also occur via Fc receptors (Allen and Boune,
1978; Isojima, 1988). In general, tail-directed ASA tend to
influence and disturb sperm progressive motility, whereas
head-directed ASA may alter fertilization by occluding binding
sites for zona pellucida binding (Bronson et al., 1984) or by
affecting motility parameters, e.g. the amplitude of lateral head
displacement (Zouari et al., 1993). The acrosome reaction,
another crucial step in human sperm function, can also be
altered by ASA (Lansford et al., 1990).
From a physiological point of view, immunological infertility
due to sperm surface antibodies can result from the effect on
sperm transport, the destruction of gametes, acrosome reaction
abnormalities, by inhibition of sperm–zona pellucida binding
or by prevention of embryo cleavage and early development
of the embryo (Bronson et al., 1984; Shushan and Schenker,
1992).
Surprisingly, spermatogenesis is apparently not affected by
the presence of IgG or IgA ASA since sperm density and/or
morphology are not influenced by the presence of these
antibodies (Haas et al., 1983; De Almeida et al., 1991).
Concerning therapy, the use of antibiotics is only worthwhile
if spermatozoal autoimmunity is caused by genitourinary
infection. Clinical benefit after immunosuppression with
steroids is only achieved after at least 6 months of therapy
(Adeghe, 1992; Peters and Coulam, 1992). Nowadays, the use
of intrauterine insemination (IUI) (after ovulation induction)
and assisted reproductive technology [in-vitro fertilization
(IVF), gamete intra-Fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI)] is more popular and probably
more effective. Recently, a few studies reported very good
results when ICSI was performed (La¨hteenma¨ki et al., 1995b;
Nagy et al., 1995) and this may have led to the premature
conclusion that IVF or ICSI is the first line treatment for male
immunological infertility.
However, until now no prospective study has been published
comparing the effectiveness of the first line IUI approach
1165
W.Ombelet et al.
versus IVF for male immunological infertility. The objective
of our prospective study was to compare success rates after
two different treatment protocols for couples with male
immunological infertility, namely IUI superovulation versus
IVF.
Materials and methods
Patients
During a 60 month period, from January 1991 until December 1995,
29 couples in our infertility programme were selected for this study.
Only patients with a history of infertility for at least 2 years and
without any major female factor such as tubal factor infertility and/
or major anovulatory disorders were included. Anovulation was
confirmed by ultrasound, basal body temperature and/or hormonal
abnormalities [oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin and progesterone]. As part of our
routine infertility investigation, all female partners had undergone
a laparoscopy, a hysterosalpingography, an endocrine evaluation
(oestradiol, LH, FSH, prolactin and progesterone) and a local (postcoital test, cervical mucus) and systemic (titre of circulating serum
ASA) immunological examination. Patients with anovulation due to
polycystic ovary syndrome were also excluded from the study. To
detect ASA in serum samples of both men and women, we used
an enzyme-linked immunosorbent technique (ELISA, Eurogenetics,
Tessenderlo, Belgium).
The male factor was evaluated by basic semen analysis of at least
two samples and the mean of these was used in this study. Special
attention was given to the volume of the ejaculate, pH, sperm
concentration, progressive motility, viability, 24 h survival and bacteriology following the WHO guidelines (WHO, 1987), except for
morphological examination, for which strict criteria were used (Kruger
et al., 1986). In our search for seminal ASA, we used the modified
mixed antiglobin reaction (MAR) for immunoglobulin G and A
(SpermMar®, Fertipro, Lotenhulle, Belgium) (Jager et al., 1978;
Andreou et al., 1995). The IgA assay became available only in 1992,
therefore some of our patients could not be tested for IgA [indicated
as not done (nd) in Table II]. The method of MAR testing did not
change during the study period and an intra-laboratory study on the
reproducibility of these tests showed very low intra- and interobserver variability (Pearson correlation coefficient 0.90 or more,
data not published).
Only men with a moderate to severe (binding to 50–100% of
spermatozoa) positive mixed antiglobulin reaction (MAR, IgG and/
or IgA) on two or more consecutive semen samples (interval: at least
1 month) were selected. If the test showed binding of .50% motile
spermatozoa, the different sites of binding (head, midpiece and/or
tail) were specified. Patients were also MAR positive (.50 %) in all
examined treatment cycles. Positive agglutination was recorded if
present. After selection of positive samples, semen was also examined
after washing (swim-up procedure or miniPercoll) and, if .0.5 3106
motile spermatozoa were recovered, two treatment options were
offered to the patients: (i) a maximum of three superovulation/IUI
cycles followed by IVF or (ii) IVF (maximum three cycles). Before
making their decision, patients were informed about the financial
costs (in favour of IUI) and the expected success rate (in favour of
IVF), according to the literature. Since we performed a prospective
study comparing success rates of repetitive IUI versus IVF, only
patients without tubal factor infertility were included in the study.
A total of 14 couples decided to start with IUI (group I), while the
remaining 15 couples underwent IVF as the first treatment (group II).
1166
Table I. Comparison of duration of infertility, female age and sperm
antibody titre (IgG and IgA defined as % of motile sperm bound) in group I
versus group II
Duration of
infertility
(months)
Female age
(years)
MAR IgG (%)
MAR IgA (%)
Group I (n 5 15)
Group II (n 5 14)
Mean (6 SD) Range
Mean (6 SD) Range
P value
42.6 6 23.9
25–96
42.1 6 26.8
25–120
NS
29.4 6 2.7
25–34
29.6 6 4.0
22–35
NS
78.0 6 17.6
29.6 6 30.4
55–100 77.2 6 17.4 55–100
0–74 26.1 6 25.1
0–70
NS
NS
NS 5 not significant, Student’s t-test
In-vitro fertilization procedure
For ovulation induction, two different regimens were used. In our
first protocol (1991–1992) we used the combination of clomiphene
citrate 50 mg (Clomid®; Merell Dow, Zaventem, Belgium or Pergotime®; Serono, Brussels, Belgium) and 75 units of human menopausal
gonadotrophin (HMG; Humegon®; Organon, the Netherlands, or
Pergonal®; Serono, Italy) daily on days 5–9. From the 10th day
of the cycle all patients attended our clinic daily for follicular
ultrasonography (Aloka®; Biomedic Belgium, Mechelen, Belgium;
endovaginal probe, 5 MHz) and serum LH, progesterone and oestradiol
determinations. Additional HMG (75 or 150 units) was given during
the next 1–4 days depending on the follicular growth and oestradiol
concentrations. HCG (5000 units, Profasi®; Serono, or Pregnyl®;
Organon) was administered when the average diameter of the dominant
follicle was ù19 mm, in the presence of an adequate serum oestradiol
response (ù800 pg/ml) and a serum oestradiol ù400 pg/ml/follicle
with a diameter ù15 mm.
In the second protocol (1993–1995) a combination of luteinizing
hormone-releasing hormone (LHRH) analogues (Buserelin®; Hoechst,
Brussels, Belgium; nasal spray 800 µg/day) and HMG was used
starting on day 2 of the cycle (short regimen). HCG was given when
the above mentioned criteria regarding diameter of the dominant
follicle and serum oestradiol concentration were met. The two different
stimulation protocols were equally distributed in both study groups.
All oocytes were retrieved under vaginal ultrasound guidance, 36 h
post-HCG. Oocytes were categorized into the following classes: postmature metaphase II, metaphase II, mature metaphase I and prophase I.
Insemination procedure
In our IUI programme, all patients received follicular stimulation
medication. The first choice treatment was the clomiphene citrate–
human chorionic gonadotrophin (CC-HCG) regimen. A daily dose
of 50 mg was given for 5 days starting on day 3–5 of the cycle.
In those patients with a history of clomiphene resistance we used
75 units of HMG daily on days 5–9 (HMG-HCG regimen). At
the 10th day of the cycle, all patients attended our clinic for
follicular ultrasonography and serum oestradiol determination.
Additional HMG (75 or 150 units) was given during the following
days if the ovarian response was insignificant. In both regimens,
HCG 5000 units were given when the average diameter of the
dominant follicle was ù19 mm. In all IUI cycles, two intrauterine
inseminations were performed on two consecutive days in the
periovulatory period. The inseminations were timed at 14–18 h
and 36–40 h post-HCG. The catheter containing washed motile
fraction was inserted up to the uterine fundus and the spermatozoa
were gently expelled into the uterine cavity. Subsequently the
Treatment of male immunological infertility
Table IIa. Overview of our 14 group I patients. Localization of antibodies (IgG and/or IgA)
Patient number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Total
96
58
56
88
86
87
55
94
100
58
100
61
85
68
MAR IgG (%)
Total
H-M-T
H
M
T
92
0
0
44
10
0
0
59
94
0
72
0
40
0
0
0
8
1
10
0
0
9
0
0
5
0
0
1
0
5
4
10
12
15
2
8
0
4
10
2
5
12
4
53
44
33
54
72
53
18
6
54
13
59
40
55
70
0
nd
14
12
22
58
0
0
70
74
35
0
nd
MAR IgA (%)
H-M-T
H
M
T
0
0
–
0
0
0
0
0
0
0
0
0
0
–
1
0
–
0
0
2
0
0
0
2
0
0
0
–
10
0
–
0
3
0
11
0
0
2
14
1
0
–
59
0
–
14
9
20
47
0
0
66
60
34
0
–
Serum ASA
Agglut.
Semen parameters
1
–
1
1
1
–
–
1
1
–
–
1
–
–
–
–
1
1
1
–
–
–
–
–
–
–
–
–
normal
ter 2
ter 1
normal
normal
oli 2–ast 1–ter 1
normal
normal
oli 1–ast 1–ter 2
ter 2
normal
oli 1
oli 1
ast 1–ter 1
H 5 head; M 5 midpiece; T 5 tail; H-M-T 5 % of sperm antibodies directed to various sites of motile spermatozoa; Oli 1 5 moderate oligozoospermia
(10–193106/ml); oli 2 5 severe oligozoospermia (,103106/ml); ast 1 5 moderate asthenozoospermia (20–49 % progressive motility); ast 2 5 severe
asthenozoospermia (,20% progressive motility); ter 1 5 moderate teratozoospermia (5–9 % normal forms); ter 2 5 severe teratozoospermia (,5% normal
forms); Serum ASA 5 serum antisperm antibodies, ELISA, positive if .75 U/ml.
Table IIb. Overview of our 15 group II patients. Localization of antibodies (IgG and/or IgA)
Patient number
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Total
58
68
70
71
90
59
93
55
58
95
100
98
60
100
84
MAR IgG (%)
Total
H-M-T
H
M
T
0
25
0
36
0
0
0
0
0
89
0
44
0
92
40
12
3
0
6
1
0
0
0
0
0
0
5
0
1
0
4
15
15
11
11
2
12
0
4
2
12
8
7
1
11
42
25
55
18
78
57
81
55
54
4
88
41
53
6
33
14
0
30
47
0
64
nd
0
38
0
18
nd
32
70
nd
MAR IgA (%)
H-M-T
H
M
T
0
0
0
0
0
0
–
0
0
0
0
–
0
0
–
0
0
0
0
0
8
–
0
7
0
0
–
1
4
–
4
0
6
0
0
13
–
0
12
0
4
–
17
22
–
10
0
24
47
0
43
–
0
19
0
14
–
14
44
–
Serum ASA
Agglut.
Semen parameters
–
–
–
1
–
–
–
–
–
–
1
1
–
1
–
–
1
–
–
–
–
1
–
–
–
–
–
–
–
–
ter 1
normal
normal
normal
ast 1–ter
ast 1–ter
ter 2
oli 2–ter
oli 1–ter
oli 2–ast
normal
normal
ter 1
normal
oli 2–ter
1
2
2
2
1–ter 2
1
H 5 head; M 5 midpiece; T 5 tail; H-M-T 5 % of sperm antibodies directed to various sites of motile spermatozoa; Oli 1 5 moderate oligozoospermia
(10–193106/ml); oli 2 5 severe oligozoospermia (,103106/ml); ast 1 5 moderate asthenozoospermia (20–49 % progressive motility); ast 2 5 severe
asthenozoospermia (,20% progressive motility); ter 1 5 moderate teratozoospermia (5–9 % normal forms); ter 2 5 severe teratozoospermia (,5% normal
forms); Serum ASA 5 serum antisperm antibodies; ELISA, positive if .75 U/ml.
catheter was withdrawn and the patient remained in the supine
position for 30 min after the insemination (Ombelet et al., 1996).
Sperm collection and washing procedure
The ejaculate was always collected in a sterile plastic jar containing
a buffer solution [10 ml of Earle’s balanced salt solution (EBSS, Life
Science International, Paisley, UK) supplemented with penicillin,
streptomycin, pyruvate and human serum albumin] in order to reduce
the number of antibodies bound to spermatozoa as mentioned in
previous studies (Boettcher et al., 1982; Harrison and Hennessey,
1984; Elder et al., 1990).
We used the conventional swim-up technique for normal samples
(count .203106/ml, total progressive motility .50%). For subnormal
samples we performed only one wash procedure, followed by centrifugation of the pellets on a miniPercoll gradient (1 ml 95% to 1 ml
50% Percoll) at 200 g for 20 min. The 95% fraction was recovered
and washed twice with EBSS 1 penicillin and pyruvate. The pellet
was resuspended in 1 ml EBSS 1 0.3% human serum albumin. For
intrauterine insemination, the samples were concentrated to 0.3 ml.
For IVF, we inseminated 100 000 spermatozoa per oocyte in the
absence of teratozoospermia. When ,10% normal forms were found
on morphological examination, oocytes were inseminated with
500 000 spermatozoa, according to the report of Oehninger et al.
(1988).
Definition of pregnancies
Only clinical pregnancies were taken into account. Clinical pregnancies were defined by a normal gestational sac at 6 weeks of pregnancy
on vaginal ultrasonography.
Statistics
Student’s t-test for unpaired samples was used to test the null
hypothesis that no significant differences existed between female age
and the mean duration of infertility in the two groups. The same
1167
W.Ombelet et al.
approach was used to check for differences between IgG and IgA
antibody titres in the two groups.
Results
The mean duration of infertility was 42.6 months (range 25–
96) for group I and 42.1 months (range 25–120) for group II
patients. There was no difference in female age between group
I (mean age: 29.4 years, range 25–34) and group II (mean
age: 29.6 years, range 22–35) (Table I). All patients suffered
from primary infertility (no previous pregnancy). One patient
in each group (group I, no. 5, group II, no. 6) suffered from
mild endometriosis; no tubal block was found in any of
the patients.
There was no significant difference in seminal IgG and IgA
titre between the two groups, neither did the site of attachment
of the sperm surface antibodies differ. Serum antibodies were
positive (ELISA .75 U/ml) in 11 patients (37.9%) and sperm
agglutination was observed in five semen samples (17.2%)
(Table IIa, Table IIb).
Sperm parameters were normal for sperm concentration,
total count, progressive motility and morphology in 12 patients
(six from each group; 41.3%). Teratozoospermia (,10% normal forms) was the most common abnormality and was found
in 15 cases (51.7%, six in group I, nine in group II).
Asthenozoospermia (,50% progressive motility) could only
be detected in six cases (20.7%, three in both groups).
Oligozoospermia (,20 3106/ml) was present in eight cases
or 27.6%, equally distributed in both groups. Oligo-asthenoteratozoospermia (OAT) was observed in three patients
(10.3%).
In group I, ten patients (64.3%) became pregnant after a
maximum of three IUI cycles with a cycle fecundity rate of
30.3%. These included one patient who miscarried in her cycle
but achieved a successful pregnancy in her second. From the
remaining five, two patients conceived during the first IVF
cycle while the other three patients were selected for ICSI
after two or three unsuccessful IVF procedures. In two patients
a very low fertilization rate (,30%) was noticed, due to poor
egg quality (increased zona thickness and presence of a
dark granulated ooplasm after assessment of oocyte maturity
according to Veeck, 1991) (Figure 1).
In group II, seven patients (46.6%) conceived during the
first treatment cycle while another seven patients became
pregnant after a second or third trial. Only one patient was
selected for ICSI because of a low fertilization rate during
three consecutive IVF cycles (Figure 1).
In this selected population the take-home baby rate (BTH)
per IUI or IVF cycle was 27.3% (9/33) and 44.4% (16/36)
respectively. Conception rate per transfer was 51.5% (17/33).
The BTH was 64.3% (9/14) after three IUI cycles versus
46.6% (7/15) and 93.3% (14/15) after one and three IVF
attempts respectively (Figure 1).
Discussion
It is generally accepted that male infertility may be caused by
the presence of sperm surface antibodies, at least if a level of
1168
Figure 1. Group I and group II patients: results after intrauterine
insemination (IUI) or in-vitro fertilization (IVF). Fertilization rate
per IVF attempt is outlined in the boxes (number of fertilized
oocytes/number of oocytes retrieved). Black boxes 5 successful
pregnancies; grey boxes 5 miscarriages; MAR 5 mixed
antiglobulin reaction.
.50% binding is reached (Bronson et al., 1984; Barratt
et al., 1992).
The immunobead test (Clarke et al., 1985) and the MAR
test for IgG and IgA (Jager et al., 1978; Andreou et al., 1995)
are the tests of choice for sperm surface antibodies. In our
study, the MAR test for IgG and IgA was used to detect male
immunological infertility.
ASA are usually detectable in seminal plasma provided that
a systemic response has occurred. Nevertheless, in clinical
practice we observed a dichotomy between local and systemic
immune response to spermatozoa and it has been reported
previously that antibodies in semen should have greater clinical
significance (Adeghe, 1992).
In our study population serum antibodies were positive in
11 patients or 37.9%. This is contradictory to the results of
Eggert-Kruse et al. (1993) who found that all MAR positive
(semen) patients were negative for circulating ASA when
assessed using an ELISA technique. The meaning of this
discrepancy is unclear and may be explained by the fact that
serum ASA values do not sufficiently reflect the immunological
situation in the semen. Serum ASA values were not helpful
in predicting success in either of our groups of patients. Sperm
agglutination was only infrequently observed (5/29 or 17.2%)
and did not correlate with the presence of asthenozoospermia
in any of our positive cases.
We also investigated the impact of immunoglobulin isotypes
(IgG and IgA) and their location on the human sperm surface
on fertilization in vivo and in vitro. We did not observe any
Treatment of male immunological infertility
predictive value concerning success rate of immunoglobulin
isotype, levels of binding or point of location on the sperm
surface in this small series. Yeh et al. (1995) described the
serious impact of the presence of sperm surface IgA on
fertilization rates in an IVF programme, only when high levels
of binding occurred. They also reported the importance of
IgM as the most significant factor with regard to fertilization,
especially when localized both on the head and the tail tip.
The present study did not investigate IgM isotypes.
It was reported previously that the proportion of spermatozoa
coated with IgG (and not IgA) antibodies became significantly
reduced when washing was performed immediately after ejacualation rather than 2 h afterwards (Adeghe, 1992). IgA may
indicate a poorer prognosis than IgG, probably because they
inhibit sperm migration through the cervical mucus and have
a greater degree of interference with fertilization (Adeghe,
1992). Since spermatozoa were always collected in a sterile
jar containing buffered medium, and since our population was
a predominantly IgG positive group, this may also explain the
good results reported from this series. Hypothetically speaking,
it seems that the use of specific sperm preparation techniques
followed by insertion of the washed motile fraction up to the
uterine fundus may overcome the detrimental influence of
sperm antibodies upon various steps of the fertilization process.
What can be the reason for male immunological infertility,
bearing in mind that, according to conventional semen analysis,
the sperm quality of most of our patients had been preserved
but they still had an infertility history of at least 2 years?
Inhibition of sperm transport within the female genital tract
is probably the most important antifertility factor in vivo
(Adeghe, 1992), suggesting that antibody-coated spermatozoa
are destroyed in utero. In-vitro studies in humans have demonstrated that spermatozoal autoantibodies induce a massive
leukocytosis and sperm disruption at the level of the fundus
uteri and the isthmic part of the oviduct (London et al., 1985).
In-vitro fertilization bypasses this adverse uterine reaction and
has therefore become a very popular and effective treatment
option for male infertility resulting from sperm surface antibodies (Haas, 1987; Palermo et al., 1989; La¨hteenma¨ki, 1993;
Rajah et al., 1993). Most studies report a lower fertilization
rate, but once fertilization has occurred, pregnancy rates are
the same or even better compared with non-immunological
IVF cases (Palermo et al., 1989; Rajah et al., 1993).
Despite the fact that IVF results are very promising in male
immunological cases, there is strong evidence that ovarian
stimulation/IUI is a reasonable first treatment option in a
substantial number of male infertility cases (Ombelet et al.,
1995). A literature survey of the few papers reporting IUI in
male immunological infertility cases leads to contradictory
results (Francavilla et al., 1992; La¨hteenma¨ki et al., 1995a).
Concerning economic aspects, published data indicate that
the costs of IVF and embryo transfer are four to seven times
the cost of a single ovarian stimulation/IUI cycle (Comhaire,
1995; Dodson, 1995; Robinson et al., 1992). In a prospective,
non-randomized, cohort study followed by meta-analysis of
different treatment procedures of assisted reproduction,
Peterson et al. (1994) concluded that a cost-benefit analysis
comparing HMG/IUI versus IVF/embryo transfer was in favour
of a first line treatment with four cycles of IUI.
Our results indicate that, with the present (limited) knowledge of male immunological infertility, treatment with ovarian
stimulation/IUI is a valuable first-choice method to use before
starting the more invasive and expensive techniques of assisted
reproduction. This study was not randomized and can be
regarded as a pilot study. Therefore, we believe that a multicentric prospective randomized study is mandatory in the near
future. Nevertheless, at the present stage, there appears to be
no reason to perform IVF or ICSI procedures as a first line
treatment in cases of male immunological infertility, even
when high levels of sperm surface antibodies prevail, at least
if .500 000 motile spermatozoa are recovered after washing.
In future, a search to determine the clinically relevant sites
of antisperm–antibody interaction will hopefully help us in
directing the treatment of male immunological infertility.
Acknowledgements
The authors wish to thank Petra Jacobs and Hilde Vanderwegen for
helping us in the production of this paper.
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Received on May 30, 1996; accepted on April 8, 1997