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Alternatives To Natural Conception

While alloimmunized women can go on to conceive naturally and have more biological children, many who have had severely affected pregnancies choose to avoid the risk. For couples who prefer to have a natural pregnancy, see Management of Alloimmunized Pregnancy, for proactive treatment options such as IVIG and plasmapheresis. Couples may also be able to participate in a clinical trial.  There are four main alternatives to natural conception: sperm donation, surrogacy, in vitro fertilization with preimplantation genetic diagnosis (IVF with PGD), and embryo adoption. It must be clearly stated that in order to avoid HDFN due to maternal alloimmunization, all donor material must be antigen negative. There is no risk of HDFN if the fetus is antigen negative. 



Sperm Donation

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. This is not the same as an antibody screen, but a specific antigen phenotype which will determine zygosity 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 additional antibodies. 

https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1002/pd.2652

https://www.uptodate.com/contents/management-of-non-rhd-red-blood-cell-alloantibodies-during-pregnancy

https://www.sciencedirect.com/science/article/pii/S1744165X08000231 

https://www.sciencedirect.com/science/article/abs/pii/S2352302616300199 



Surrogacy

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’. 

https://www.uptodate.com/contents/management-of-pregnancy-complicated-by-rhd-alloimmunization 

https://www.sciencedirect.com/science/article/abs/pii/S2352302616300199 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280450/ 



IVF with PGD

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.

https://academic.oup.com/humrep/article/20/3/697/2356451

https://www.sciencedirect.com/science/article/pii/S0015028203011567 

https://www.rbmojournal.com/article/S1472-6483(10)62300-0/abstract 

https://journals.lww.com/greenjournal/FullText/2012/02000/Preimplantation_Genetic_Diagnosis_for_Fetal.20.aspx 

https://www.sciencedirect.com/science/article/pii/S0301211509002449




Embryo Adoption

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. 


https://www.sciencedirect.com/science/article/abs/pii/S0037196305000600
https://academic.oup.com/molehr/article/2/1/60/1075251
https://www.sciencedirect.com/science/article/abs/pii/S1472648310611455 

https://academic.oup.com/humupd/article/16/6/704/741844 

https://www.ncbi.nlm.nih.gov/books/NBK2270/