Background/Purpose:

Infertility is a
common condition, affecting 8-12% of couples in childbearing age. Even
though the association of aPL with infertility is highly debated, infertile
women are commonly screened for anti-phospholipid antibodies (aPL). Therefore,
the aim of this work was to accurately review available evidence.

Methods:

A systematic
PubMed search was conducted to retrieve papers addressing the: i) association
between aPL positivity and infertility, ii) positivity rate of criteria and non
criteria aPL in infertile women and iii) association between aPL positivity and
ART outcome. aPL positivity rates in infertile women and controls were calculated
as median (25-75 percentiles); differences in aPL positivity rate between
patients and controls were evaluated by Wilcoxon matched-pair test. The
strength of association between aPL positivity and both infertility and outcome
of assisted reproduction technologies (ART) were expressed as the rate of
studies confirming a positive association.

Results:

A total of 39
papers were considered in this critical analysis. There was a wide
heterogeneity in the selection of study and control populations; only 10% of
the studies presented a prospective design. aPL cut-offs conforming to
international guidelines were used in less than 25% of studies; aPL positivity
was confirmed in 11% of studies. Approximately half of the considered studies
assessed non criteria aPL tests. i) According
to our best estimates, the overall positivity rate of criteria aPL tests is 6%
(2-8.9) among infertile women and 1% (0-2.15) among controls. Non criteria aPL
tests were estimated to be positive in 3% (1.5-9) of study women and in 2%
(1-7) of controls. Table 1 reports the calculated frequencies of each of the considered tests in
patients and controls. A significant difference in the positivity
rate of patients versus controls emerged for anti-cardiolipin antibodies (aCL)
only (p<0.00001, 95% CI 3.35-8.50). ii) The association rates between each aPL test and
infertility are detailed in Table 2. iii) Only 5 of the relevant 18 studies (27.7%) reported a
detrimental effect of aPL on ART outcome. Of these studies, 4 assayed only
criteria aPL tests and one aCL plus non-criteria aPL tests.

Conclusion:

According to our
literature revision, aPL are more frequently detected among infertile women than
controls; conversely, the association between aPL and ART outcome is not
supported by most studies. Data inconsistencies might be ascribed to the lack
of a true association or to literature limitations; well-designed studies are
warranted to produce strong evidence-based recommendations.

Table 1

Table 2