fertilitzation rate in couples with ui
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8/13/2019 Fertilitzation Rate in Couples With UI
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Human Reproduction vol 7 no.2 pp.223-226, 1992
Fertilization rate in couples with unexplained infertility
A.I.Mackenna 1, F.Zegers-Hochschild,E.O.Fernandez, C.V.Fabres, C.A.Huidobro,J.A.Prado, L.S.Roblero, E.L.Altieri,A.R.Guadarrama and T.H.Lopez
Department of Obstetrics and Gynaecology, Climca Las Condes,Institute Chileno de Medicina Reproductiva, Santiago, Chile
'Present address and address for correspondence: The University ofSheffield, Department of Obstetrics and Gynaecology, JessopHospital for Wom en, Sheffield S3 7RE, UK
A group of 24 couples with unexplained infertility wasscheduled for in-vitro fertilization and tuba] embryo transfer
between May 1989 and September 1990. In the same period,
in-vitro fertilization and intrauterine transfer of embryos was
planned in a control grou p of women with tubal infertility.
The m ean age and d uration of infertility were similar in both
groups and the sam e scheme of ovarian stimulation was used.
No statistically significant difference was obtained comparing
oestradiol levels and numbers of mature oocytes retrieved
between the group of patients with unexplained infertility and
those with tubal infertility. The fertilization rate of the oocytes
obtained from women with unexplained infertility (60.4%)
was significantly lower P < 0.001) than that of the oocytes
obtained from patients with tubal infertility (87.3%). Therewas n o statistically significant difference in the cleavage rates
between patients with unexplained infertility and those with
tubal infertility. It is concluded that lack of fertilization is
an unexplored cause of infertility in couples with unexplained
infertility.
Key words: unexplained infertility/fertilization rate
Introduction
Unexplained infertility refers to those couples who have failed
to establish a pregnancy despite no cause of infertility being
identified or after correction of the factor presumed to be
responsible for infertility (Moghissi and Wallach, 1983). Its
reported incidence has varied between 6% and 27% (Moghissi
and W allach, 1983). This wide variability inevitably depends on
the methodology used to reach the diagnosis. Clearly, the more
exhaustive the evaluation of the infertile couple, the less will be
the possibility of reaching this diagnosis because more causes
of infertility can be identified (Navot et al., 1988).
Even when a com plete evaluation of the couple is performed,
there are some processes necessary for conception which are
inaccessible to traditional diagnostic methods and therefore, in
some cases, the cause of infertility remains unknown. Two
important unexplored events in human reproduction are sperm
transport through the upper genital tract (Taylor and Kredentser,
1989) and in-vivo fertilization.
In-vitro gamete interaction seems to be a good alternative for
the treatment of unexplained infertility (Navot et al., 1988;
Audibert et al., 1989), as well as for the investigation of this
condition (Trounson et al., 1980). However, the latter advantage
of in-vitro fertilization procedures has not received enough
attention.
The main objective of this study is to evaluate the in-vitro
fertilization rate in couples with unexplained infertility.
Materials and methods
A study group of 24 women with unexplained infertility was
scheduled for in-vitro fertilization and tubal embryo transfer
between May 1989 and September 1990 at the Unit of
Reproductive Medicine of Clinica Las Condes (Santiago, Chile).
The mean age of the patients was 33 (SD = 3.1) years and they
had a mean of 6 (SD = 1.3) years of infertility. A com plete
diagnostic work-up of the infertile couple was performed before
the procedure was indicated and for the diagnosis of unexplained
infertility, the findings had to be entirely normal. The analysisincluded ultrasound monitoring of follicular growth and samples
of cervical mucus, obtained in the fertile period, for scoring
(WH O, 1987) and for in-vitro spe rm -m uc us interaction (WHO,
1987). Semen analysis and the sperm mixed antiglobulin reaction
(MAR)-test, as well as homologous and heterologous in-vitro
penetration tests were performed, considering as normal
parameters those described by the World Health Organization
(1987). Two blood samples for measurement of prolactin and
progesterone were obtained in the mid-luteal phase. Results of
hysterosalpingography, hysteroscopy and laparoscopy performed
in all patients were normal.
Simultaneously a control group of 44 women with tubal
infertility was scheduled for in-vitro fertilization and intrauterineembryo transfer (IVF). These were all the patients with tuba
infertility and whose husbands had normal semen parameters
Table I. Age and duration
Unexplained infertility
Tubal infertility
of infertility
Women
(n)
24
44
Age-f(SD)
3 3 ( 3 . 1 ) '
33 (3.3)'
Years of infertility* ( S D )
6 (1 3)b
7 ( 1 . 9 )b
a/b = NS
© Oxford University Press 223
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A.I.Mackenna el al.
TaWe D. N umb er of follicles S: 16
undergoing the same superovulation
Unexplained infertility*
Tubal infertility
mm, oestradiol values andscheme
Women
(")
23
44,
number of mature oocytes
Folliclesa 16 mm onday of HCGJ ( S D )
6 8 \2 f
7 0 (1 7)1
retrieved in patients with unexplained
Oestradiol/folliclea 16 mm on dayof HCG (pmol/l),f (SD)
1440 (540)"
1350 (560)"
infertility or tubal infertility
Mature oocytes
retrieved
x (SD)
6. 8 (1.3)c
7.5 (1.8)c
*24 minus 1 empty follicle syndrome .HCG = human chorionic gonadotrophin.a/b/c = NS.
(W HO , 1987) who were treated in the same period of time. Th e
mean age of these patients was 33 (SD = 3.3) years and they
had a mean of 7 (SD = 1.9) year s of infertility.
The same ovulation induction scheme was used in the study
and control groups for induction of multiple follicular maturation.
Leuprolide acetate (Lupron, Abbott Laboratories), human
menopausal gonadotrophin (Pergonal, Serono Laboratories) and
human chorionic gonadotrophin (HCG; Profasi, Serono
Laboratories) were used. Transvaginal ultrasound (Aloka, model
630, 5.0 MHz probe) was performed and daily blood samples
were taken for oestradiol measurement starting on day 6 of the
treatment cycle. Oocyte retrieval was performed, by transvaginal
aspiration of the follicles, 34 —36 h after the HCG injection.
Oocyte quality was assessed by light microscopy, considering
mature oocytes to be those with an expanded cumulus, radiant
corona, distinct zona pellucida, clear ooplasm and also expanded
granulosa cells. Only mature oocytes were inseminated with
100 000 spermatozoa each, thus ensuring these factors were not
variables interfering with the fertilization rate. Spermatozoa were
prepared using a standard swim-up technique (Cohen ex al., 1985)
and the mean final sperm count was 31.1 (range = 2. 4- 79 .2 )
million and 26.1 (range = 2.0—73.0) million in the unexplainedand tubal infertility groups respectively (NS). Fertilization was
assessed 18 h later and, if cleavage was observed, 48 - 5 0 h after
insemination tubal or intrauterine embryo transfer was performed.
The luteal phase was supplemented with daily intramuscular
injections of progesterone (50 mg), and blood samples for HCG
measurement were obtained on days +12, +15, +18 and +21
after transfer. For calculation of the pregnancy rate, all
pregnancies confirmed by sonographic evidence of a gestational
sac and embryo were counted.
For statistical analysis, Student's f-test, Fisher's exact test, chi-
square test, Mann -W hit ne y U test and power analysis were used.
The level of statistical significance was fixed at P < 0.05.
Results
No statistically significant difference was obtained comparing the
age and duration of infertility between the two groups (Table I).
The data of Table II provide a comparison of the number of
follicles > 16 mm in diame ter and the oestradiol levels on the
day of the HC G injection, and show no significant differences
between the study and control groups. In the group with
unexplained infertility, oocytes were obtained from 66.7%
(188/282) of the aspirated follicles compared with 71.3%
TaWe HI. Fertilization
Unexplained infertility*
Tubal infertility
rate and cleavage rate
Inseminatedoocytes
149
292
Fertilization
rate
(%)
60.4 '
87 3"
Cleavage
rate
(%)
92.2"
93.7"
2co
3tn
a>
5
25
J
•24 minus 1 empty follicle syndrome,a = P < 00 01 , b = NS.
H
75
Unexplainedinfertility
Tubal
infertility
Fig. 1. Fertilization rate for each couple treated in a group of
patients with unexplained infertility (n = 23. median = 70% andrange = 0-100%) or tubal infertility (n = 44, median = 90%and range = 0-1 00 %) Ma nn-W hitney U test P < 0.001.
(381/534) successful retrievals in the group with tubal infertility
(NS). No statistically significant difference was observed
comparing the mean numbers of mature oocytes retrieved bet-
ween the two groups. One patient with the diagnosis of
unexplained infertility presented empty follicle syndrome (Coulam
et al., 1986) and no oocytes were obtained after transvaginal
aspiration of 10 follicles.
224
y g
y ,
p
j
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Unexplained infertility
A total of 149 mature oocytes from the group with unexplained
infertility were inseminated and in 90 of them fertilization was
observed (60 .4%); in the control group, 292 mature oocytes were
inseminated and 255 of them fertilized (87.3% ) (Table HI). This
difference is highly significant (P < 0.001). The cleavage rate
(the percentage of fertilized oocytes undergoing cleavage) was
similar in the two groups.
The rate of failed fertilization (patients who did not fertilize
any of the inseminated oocytes) was 13% (3/23) in the groupwith unexplained infertility and 4.5 % (2/44) in the control group
(NS). Figure shows the fertilization rate for each couple treated.
There is a highly significant difference between the two groups
(P < 0.001).
Twenty women with unexplained infertility underwent tubal
embryo replacement and intrauterine embryo transfer was
performed in 42 patients with tubal infertility. A clinical
pregnancy rate of 40% (8/20) and 33% (14/42) was observed
in the unexplained and tubal infertility groups respectively. Only
one first trimester abortion was observed in both groups occurring
in a patient with unexplained infertility.
Discussion
In comparison with patients with tubal infertility, the fertilization
rate in couples with unexplained infertility was significantly lower
(unexplained = 60.4% and tubal = 87.3%). Similar results have
been reported by Navot et al. (1988) and Audibert et al. (1989).
Since there were no differences between the two groups with
respect to the age of the patients, duration of infertility, number
of follicles developed, oestradiol values, numbers of oocytes
retrieved and light microscopic characterization of the oocytes,
it is resonable to conclude that in couples with unexplained
infertility there is an unknown factor which decreases the
fertilization rate. Another unexplored, but uncommon, cause of
unexplained infertility could be the empty follicle syndrome(Coulam etai., 1986).
Recently, Calvo et al. (1989), assessing the ability in 15 men
with unexplained infertility of capacitated spermatozoa to undergo
the acrosome reaction, found a sub-group of six with a lack of
acrosome reaction; Fenichel et al. (1991) concluded that an
impaired acrosomal status can be associated with unexplained
unsuccessful fertilization. Further studies must be developed to
assess whether the lack of fertilization demonstrated in couples
with unexplained infertility is due to functional defects in
spermatozoa and/or to oocyte defects.
When fertilization occurred, the cleavage rate was similar in
the unexplained and tubal groups of infertile p atients, suggestingthat fertilization rather than the subsequent development of the
fertilized oocyte is altered. Moreover, other authors using
intrauterine embryo transfer for both groups of patients have
observed that the implantation rate is also similar in women with
tubal or unexplained infertility (Audibert et al., 1989). In the
present study, it is impossible to compare both groups in terms
of pregnancy rate because different routes of embryo replacement
were used.
Although there was a trend towards a higher rate of failed
fertilization in the group with unexplained infertility, with the
number of patients included in this study (total = 67) this failed
to reach the level of statistical significance. Power analysis shows
that if this trend was maintained, 212 patients would be needed
to obtain a statistically significant difference (P < 0.05 ). On the
other hand, looking at the fertilization rate for each couple treated,
a statistically significant difference was obtained between the
study and control groups. As shown in Figure 1, most of the
couples with unexplained infertility had low fertihzation rates and
the majority of patients with tubal infertility had high fertilization
rates.
In spite of failing to identify a treatable condition, various
empirical treatments can be used in couples with unexplained
infertility (Chan and Ratnam, 1989). The good results obtained
in this series com pare favourably with the results in other series,
in which assisted fertilization techniques have also been used
(Leeton etai, 1987; Navot et al., 1988; Wong et al., 1988;
Audibert etai., 1989; Devroey etai, 1989; Sharma etai.,
1991). Th ese results are probably attributable to either the greater
chance of obtaining fertilization when more than one oocyte is
inseminated, or to by-passing the impaired sperm transport
through the upper genital tract, as has been suggested by Cefalu
et al. (1988) and Templeton et al. (1982). On the other hand,
Ramsewak et al. (1990) have demonstrated that spermatozoa areconsistently able to traverse the reproductive ract in patients with
unexplained infertility. This finding, however, does not
necessarily imply that the spermatozoa were competent to achieve
fertilization. The interaction between the spermatozoa and the
upper human female tract is a matter of present and future
research (Barratt and Cooke, 1991).
It is concluded that lack of fertilization is an unexp lored cause
of infertility in couples with unexplained infertility. This study
also suggests that in-vitro fertilization procedures have an
important role in both the investigation and the treatment of these
infertile couples.
Acknowledgements
We are very grateful for the advice given by Professor I.D.Cooke andDr J.P.Balmaceda.
References
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