Hum. Reprod. Advance Access originally published online on October 2, 2007
Human Reproduction 2007 22(11):3043-3044; doi:10.1093/humrep/dem163
Letters to the Editor |
Antiphospholipid antibodies in serum and follicular fluid: is there a correlation with IVF implantation failure?
1 Department of Obstetrics and Gynecology, Specialized Clinical Science, Tokai University School of Medicine, Kanagawa, Japan 2 HLA-Vascular Biology Laboratory, St Francis Hospital, Beech Grove, IN, USA
3 Correspondence address. Tel: +81-463-93-1121; Fax: +81-463-91-4343; E-mail: hide-m{at}is.icc.u-tokai.ac.jp
We have read the paper of Buckingham et al. (2006)
with considerable interest because we have recently published a related study (Matsubayashi et al., 2006). Buckingham et al. (2006) reported that antiphospholipid antibodies (aPLs) do not appear selectively concentrated in follicular fluids and, when present, do not adversely affect the reproductive outcome of women undergoing in vitro fertilization (IVF) procedures. Their conclusion is at variance with our findings (Matsubayashi et al., 2006). Our studies focused upon the finding of immunoglobulin G (IgG)–aPLs in follicular fluids and the relationship between these aPLs and low-fertilization rates.
To our knowledge, there are but two additional published studies describing aPLs in the follicular fluids of IVF patients (El-Roeiy et al., 1987; Nip et al., 1995). We have compared and summarized the findings of all four studies in the Table. Each study showed that IgG–aPLs were detected in follicular fluids, whereas IgM–aPLs were detected in one only. In reference to immunoglobulin levels, El-Roeiy et al. (1987) reported the total IgG, IgM and IgA concentrations in follicular fluids were 
1/2, 1/10 and 1/2 of those in sera, respectively. He was the only investigator to show IgM in two patients and IgA in one patient with increased positive levels in follicular fluids when compared with corresponding serum levels. Nip et al. (1995) also showed that IgG or IgA values in follicular fluids were lower, ranging from 55 to 93% of the corresponding sera with no IgM was detected. All four studies agree that aPLs are not selectively concentrated in follicular fluids and that there appears to be no diagnostic value in screening follicular fluids for aPLs.
We cannot directly compare our study with the others because our study included only IVF-failure patients and excluded intracytoplasmic sperm injection (ICSI) patients, the latter may include more severe unexplained-female-factor patients than found in the others. If, however, Buckingham had excluded ICSI patients and focused solely on IgG–aPLs and IVF-failure, fertilization rates would have decreased significantly. Moreover, aspirin was administered to all women in the Buckingham study, which may improve the IVF success rate in aPL-positive patients. Our study did not use aspirin or other confounding agents.
In contrast to the other three studies, we observed a significant relationship between fertilization rate and IgG–aPLs found in the follicular fluids. The observation by Nip et al. (1995) that showed no pregnancies to occur in patients with IgG–aCL in follicular fluids supports our findings. Thus, we propose that follicular fluid IgG–aPLs may be associated with reduced fertility because of direct effects upon oocytes and/or embryos. The rare finding of IgM–aPLs in follicular fluids suggests that assessment for IgM may be excluded in future studies.
Due to limited sample size numbers shown in the Table 1, none reached statistical significance in terms of pregnancy rates and follicular fluid aPLs. Indeed, Buckingham's analyses suggested that data from more than 1240 women would be needed to provide a statistically valid conclusion. We agree with this appraisement and propose that a multi-centre study for follicular fluid aPLs be contemplated. We would emphasize that IgG–aPLs should be the major focus. Such a collaborative study would be able to draw meaningful conclusions regarding the pathognomonic effects of aPLs in follicular fluids.
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References
Buckingham KL, Stone PR, Smith JF, Chamley LW. Antiphospholipid antibodies in serum and follicular fluid: is there a correlation with IVF implantation failure? Hum Reprod (2006) 21:728–734.
El-Roeiy A, Gleicher N, Friberg J, Confino E, Dudkiewicz A. Correlation between peripheral blood and follicular fluid autoantibodies and impact on in vitro fertilization. Obstet Gynecol (1987) 70:163–170.[Web of Science][Medline]
Matsubayashi H, Sugi T, Arai T, Shida M, Kondo A, Suzuki T, Izumi S, McIntyre JA. IgG antiphospholipid antibodies in follicular fluid of IVF-ET patients are related to low fertilization rate of their oocytes. Am J Reprod Immunol (2006) 55:341–348.[Medline]
Nip MM, Taylor PV, Rutherford AJ, Hancock KW. Autoantibodies and antisperm antibodies in sera and follicular fluids of infertile patients; relation to reproductive outcome after in-vitro fertilization. Hum Reprod (1995) 10:2564–2569.
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