FERTILITY AND STERILITY
Vol. 57, No.2, February 1992
Copyright © 1992 The American Fertility Society
Printed on
acid~free
paper in U.S.A.
Immunotherapy with paternal lymphocytes preceding in vitro fertilization-embryo transfer for patients with repeated failure of embryo transfer
Isao Hasegawa, M.D.* Hiromitsu Tani, M.D. Koichi Takakuwa, M.D.
Kiyoshi Yamada, M.D. Koji Kanazawa, M.D. Kenichi Tanaka, M.D.
Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan
Some failures of embryo transfer (ET) after in vitro fertilization (IVF), especially in cases with repeatedly unsuccessful ET, are thought to be because of occult abortion (1). We have previously reported that a proportion of infertile couples with repeatedly unsuccessful ET showed close histocompatibility similar to those of primary recurrent aborters (2). Recently, it has been noted that immunotherapy with paternal lymphocytes achieves a high efficacy in preventing subsequent abortion in women with primary recurrent abortion of unknown cause (3,4), which was mediated by facilitating immune reactions including blocking antibody (3). Based on the immunological similarity to primary recurrent aborters, a possibility that this immunotherapy could improve the pregnancy success rate of IVFET has been suggested (1). To substantiate the hypothesis, we applied immunotherapy preceding IVFET to three women with three to four successive failures of ET who showed close histocompatibility with the husband. Blocking antibody was induced by immunotherapy, and the subsequent new IVFET was successful in one woman. MATERIALS AND METHODS Patients
Three patients with infertility were included in this study as listed in Table 1. The cause of infertility
Received June 24, 1991; revised and accepted September 25, 1991. * Reprint requests and present address: Isao Hasegawa, M.D., Department of Obstetrics and Gynecology, Akita Red Cross Hospital, 1-4-36 Nakadori, Akita 010, Japan. Vol. 57, No.2, February 1992
in each patient was definite tubal factor (bilateral occlusion or hydrosalpinx). None ofthem had other causes of infertility including male factor. All of these patients had received IVF -ET on three or four occasions according to the previously described protocol (2). The IVF-ET had been unsuccessful despite the transfer of two or more embryos with normal morphological features. In addition, these patients and their husbands showed no known etiology of implantation failure such as uterine anomaly, hormonal deficiency, infectious diseases, and chromosomal abnormality. Immunological Assays
Histocompatibility between couples was evaluated by a new lymphocyte-serotyping method reported previously (2). In brief, lymphocytes from each of the couples were subjected to cytotoxicity assay against 16 nonanti-human leucocyte antigen (HLA) alloantisera derived from secondary recurrent aborters, and the difference of reactive patterns between couples was then analyzed and expressed as a total disparity value. An intercouple total disparity value of
Vol. 57, No.2, February 1992
Copyright © 1992 The American Fertility Society
Printed on
acid~free
paper in U.S.A.
Immunotherapy with paternal lymphocytes preceding in vitro fertilization-embryo transfer for patients with repeated failure of embryo transfer
Isao Hasegawa, M.D.* Hiromitsu Tani, M.D. Koichi Takakuwa, M.D.
Kiyoshi Yamada, M.D. Koji Kanazawa, M.D. Kenichi Tanaka, M.D.
Department of Obstetrics and Gynecology, Niigata University School of Medicine, Niigata, Japan
Some failures of embryo transfer (ET) after in vitro fertilization (IVF), especially in cases with repeatedly unsuccessful ET, are thought to be because of occult abortion (1). We have previously reported that a proportion of infertile couples with repeatedly unsuccessful ET showed close histocompatibility similar to those of primary recurrent aborters (2). Recently, it has been noted that immunotherapy with paternal lymphocytes achieves a high efficacy in preventing subsequent abortion in women with primary recurrent abortion of unknown cause (3,4), which was mediated by facilitating immune reactions including blocking antibody (3). Based on the immunological similarity to primary recurrent aborters, a possibility that this immunotherapy could improve the pregnancy success rate of IVFET has been suggested (1). To substantiate the hypothesis, we applied immunotherapy preceding IVFET to three women with three to four successive failures of ET who showed close histocompatibility with the husband. Blocking antibody was induced by immunotherapy, and the subsequent new IVFET was successful in one woman. MATERIALS AND METHODS Patients
Three patients with infertility were included in this study as listed in Table 1. The cause of infertility
Received June 24, 1991; revised and accepted September 25, 1991. * Reprint requests and present address: Isao Hasegawa, M.D., Department of Obstetrics and Gynecology, Akita Red Cross Hospital, 1-4-36 Nakadori, Akita 010, Japan. Vol. 57, No.2, February 1992
in each patient was definite tubal factor (bilateral occlusion or hydrosalpinx). None ofthem had other causes of infertility including male factor. All of these patients had received IVF -ET on three or four occasions according to the previously described protocol (2). The IVF-ET had been unsuccessful despite the transfer of two or more embryos with normal morphological features. In addition, these patients and their husbands showed no known etiology of implantation failure such as uterine anomaly, hormonal deficiency, infectious diseases, and chromosomal abnormality. Immunological Assays
Histocompatibility between couples was evaluated by a new lymphocyte-serotyping method reported previously (2). In brief, lymphocytes from each of the couples were subjected to cytotoxicity assay against 16 nonanti-human leucocyte antigen (HLA) alloantisera derived from secondary recurrent aborters, and the difference of reactive patterns between couples was then analyzed and expressed as a total disparity value. An intercouple total disparity value of
