Out of all the options for conceiving a child without the offending antigen, sperm donation is perhaps the easiest and most effective. Costs for sperm donation can be as low as $500. Prior to insemination the donor must have his antigen status determined via antigen phenotype. He must be negative for the antigen (a woman with anti-fya needs an fya- donor). This is not the same as an antibody screen, but a specific antigen phenotype which will determine if he is homozygous, heterozygous, or negative for the antigen that matches the maternal antibody. While it is not required, some providers attempt to match the D, K, c, and E status of the donor to the mother to prevent development of anti-D, anti-K, anti-c, and anti-E antibodies during pregnancy.

Additional Reading:

Molecular determination of RHD zygosity:predicting risk of hemolytic disease of the fetus and newborn related to anti‐D Management of Non-RhD Red Blood Cell Alloantibodies During Pregnancy Fetal anemia due to non-Rhesus-D red-cell alloimmunization Red-blood-cell alloimmunisation in relation to antigens’ exposure and their immunogenicity: a cohort study

If a couple wishes to produce a 100% biological child without the risk of HDFN, surrogacy may be considered. For this method eggs and sperm are extracted from the couple and implanted into a surrogate. There are few requirements in regards to alloimmunization with this method. The surrogate must be tested for antibodies prior to implantation. To avoid HDFN due to ABO incompatibility, it would be wise to match the surrogate’s blood type to the fetus’.

Additional Reading:

Management of pregnancy complicated by RhD alloimmunization Red-blood-cell alloimmunisation in relation to antigens’ exposure and their immunogenicity: a cohort study The Influence of Clinical and Biological Factors on Transfusion-Associated Non-ABO Antigen Alloimmunization: Responders, Hyper-Responders, and Non-Responders

For women with severe alloantibodies, the cost of pursuing assisted reproductive technology outweighs the physical and psychological risks of dealing with an alloimmunized pregnancy. These women may choose to undergo IVF with PGD in order to conceive a 100% biological child with their partner. This technology only works if the father is heterozygous (Kk in the case of anti-Kell) for the antigen. If the father is homozygous for the antigen (KK), then all children will be K positive and this method will not work. If the father is negative for the antigen (kk), then no assistance is needed as all children will be negative for the antigen and completely safe. It is worthwhile to repeat the father’s antigen phenotype to confirm the results before undergoing the IVF procedure. IVF with PGD has been used to successfully avoid incompatibility due to maternal anti-D and anti-Kell, two of the most severe causes of HDFN. It has also been used to avoid maternal fetal incompatibility for those with platelet alloimmunization and the resulting FNAIT. The biggest barriers to this method are the financial cost and the father’s antigen status.

Family Story: Tracey and Alex

Additional Reading:

The role of preimplantation genetic diagnosis in the management of severe rhesus alloimmunization Preimplantation genetic diagnosis for the Kell genotype Preimplantation genetic diagnosis as a strategy to prevent a fetomaternal incompatibility for a highly immunogenic platelet antigen causing severe Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) Preimplantation Genetic Diagnosis for Fetal Neonatal Alloimmune Thrombocytopenia Due to Antihuman Platelet Antigen Maternal Antibodies Preimplantation genetic diagnosis: State of the art

Embryo adoption involves the use of frozen embryos from other couples (not the couple trying to conceive). Additional testing is required as both the maternal donor and paternal donor must be negative for the mother’s corresponding antigen. Embryo adoption can be done with or without PGD. For those choosing to use PGD, it may be reassuring to note that many providers and parents feel that PGD is a good choice for ensuring children will not be affected by the disease they are trying to avoid. It is important to note that the entire embryo will be allogeneic to the mother. Once a woman has one alloantibody she is more likely to develop another. The mother should be checked with an antibody screen to ensure no additional antibodies have developed during pregnancy. While this field is new and growing and there are few absolute guidelines, in the case of an alloimmunized mother it may be a good idea to try and match the D, Kell, C/c and E/e status of the embryo to the mother.

Additional Reading:

Red Blood Cell Alloimmunization in Pregnancy Diagnosing and preventing inherited diseases: Management of Rhesus isoimmunization by preimplantation genetic diagnosis PGD patients’ and providers’ attitudes to the use and regulation of preimplantation genetic diagnosis Clinical and immunologic aspects of egg donation pregnancies: a systematic review The Kell blood group