Public policy recommendations concerning prenatal adoption of frozen embryos in light of fetal microchimerism.

• Author: Scarnecchia, D. Brian

No one is quite sure why women on average live longer than men. (1) Immunologists suggest that one answer may be found in small pockets or colonies of fetal stem cells that traffic into the body of pregnant women. (2) Normally, foreign cells that enter a person's body are detected, engulfed, and destroyed by T-cell lymphocytes. (3) However, due to the "'immunological paradox of pregnancy,'" a woman's body when pregnant generally does not attack but, rather, accommodates her own embryo (comprised of foreign cells). (4) On the other hand, in cases of preeclampsia, a woman's body rejects the embryo she conceived due to an "immunologic intolerance between maternal and fetal tissues." (5) This Article attempts to understand these puzzling biological processes, their ethical significance, and their import for law and public policy concerning the prenatal adoption of frozen embryos.

Part I notes that these fetal microchimeric cells bearing the genetic heritage of the father migrate across the placental barrier during pregnancy and then differentiate into male tissue cells within the mother's body that persist within her for her whole life. The invasion and colonization of maternal tissue and organs with chimeric cells bearing the genetic heritage of non-spouse father in cases of heterologous prenatal embryo adoption (6) would seem to violate spousal one-flesh union. (7) Thus, Part II shows how recent immunological studies corroborate an interpretation of Dignitas Personae that views heterologous prenatal embryo adoption as morally illicit. It is wrong not merely because of possible negative medical, legal, or social circumstances that may attend it. Rather, it is wrong because it violates spousal one-flesh union, which is an intrinsic evil. Fetal microchimerism substantiates that heterologous prenatal adoption, even if done with a noble intention to save the child's life, is incapable of being oriented to God or human flourishing. In this respect it is not dissimilar from heterologous in vitro fertilization or surrogate motherhood. However, homologous embryo transfer accompanied by prior seminal priming through spousal acts of conjugal love, is morally licit because the essential role of the father in establishing the pregnancy of wife is not substituted, but merely assisted, by the acts of medical technicians. Therefore, Part III contends that law and public policy should not allow heterologous embryo adoption. However, because placental immune suppression and fetal microchimerism do not violate the one-flesh union of spouses who repent of homologous in vitro fertilization, public policy should favor homologous embryo transfer so long as in vitro fertilization remains legal.

1. BIOLOGY, PREGNANCY, AND THE MATERNAL IMMUNE SYSTEM (8)

   Why are some women prone to life-threatening preeclampsia? (9) According to immunologists, the answer involves the role of semen in sustaining a healthy pregnancy. The working hypothesis among many immunologists is that maternal T-cells, her so-called immunological border guards, (10) are first "primed" by repeated deposits of seminal fluid during sexual intercourse with the same man: "insemination is hypothesized to constitute a 'priming' event, acting to induce maternal immune tolerance to paternal transplantation antigens, many of which are present in semen and shared by the conceptus." (11) These genetically-specific male antigens located in semen reprogram the maternal T-cell lymphocytes (12) to accept cells with this particular antigen, which would normally be rejected by the mother's immune system as foreign invader cells. However, due to this seminal priming, maternal lymphocytes treat the embryo, which present the same antigen-identification as found in the semen, as native cells: "[S]emen may contribute to the induction of immunological tolerance towards paternal transplantation antigens, thereby favouring the survival of the semi-allogeneic conceptus." (13)

   Consequently, in a successful pregnancy, the maternal T-cell lymphocytes actively assist the conceptus exhibiting the same antigen-presenting cells previously encountered in the semen, rather than arresting and attacking them as foreign invaders:

   [E]xposure of the female reproductive tract to seminal TGF[beta] [transforming growth factor beta] initiates an influx of antigen-presenting cells that sample ejaculate antigens and subsequently activate lymphocyte populations in lymph nodes draining the uterus.... TGF[beta] is implicated as a potent immune deviating agent in the uterus. Thus, the processing of paternal transplantation antigens in a milieu containing high levels of TGF[beta] of seminal plasma origin may result in the generation of hyporesponsiveness in paternal antigen-specific T-lymphocytes. It is reasonable to postulate that, upon re-encounter with conceptus antigens, these regulator or effector T-cells might contribute to an immunological environment favouring successful implantation and optimal placental growth. (14) This "tolerogenic" (suppressed) immune response produced by seminal antigens was first noted in mice. (15) Additional animal studies confirmed that it was semen--and not the physical act of copulation--that initiated the "inflammatory cascade" of immunologic tolerance that consequently improved litter size. (16) Providing further confirmation of the indispensable role of seminal fluid, women with high rates of miscarriage were also shown to experience significant improvement with embryo implantation after seminal plasma pessaries were applied. (17) Also, women exposed to the semen of their male partners through sexual intercourse showed significantly higher rates of viable embryos at six to eight weeks of gestation after embryo transfer following in vitro fertilization. (18)

   However, this tolerogenic priming effect on a woman's immune system, allowing for improvement in embryo implantation rates, appears to be lost if she changes male partners. Because preeelampsia seems to be caused by an overly aggressive maternal immune response toward paternal antigens detected in the embryo, (19) researchers argue that the genesis of this pathology is linked to a woman's immunological memory of particularized antigens in male semen: "[T]he observations of partner specificity and cumulative benefit of semen exposure imply that immunological 'memory' to partner's antigens may be programmed at insemination." (20)

   Studies show that when a woman's immune system is not primed and has no immunological memory of particularized antigens in male semen due to withdrawal or barrier method contraceptives, those embryos that are conceived frequently fail to implant. One study demonstrated that "single women who used barrier contraception had a 2-fold higher risk of developing preeclampsia." (21) Researchers at Chapel Hill, North Carolina Memorial Hospital, conducted an unconditional logistic regression analysis that indicated "a 2.37-fold (95% confidence interval, 1.01 to 5.58) increased risk of preeclampsia for users of contraceptives that prevent exposure to [male ejaculate]." (22) In another study, a 2.4-fold increased risk of preeclampsia was concluded for users of contraceptive methods that inhibit interaction with male semen. (23) Yet another study found "a 2.52-fold (with 95% confidence interval, 1.17 to 5.44, p

   Other researchers have demonstrated "that prevalence of preeclampsia in primigravida women is associated with weekly number of coitus before conception and the use of barrier contraceptive method." (25) Dr. Jon Einarsson, an obstetrician/gynecologist at Baylor College of Medicine in Houston, Texas, reporting to the American College of Obstetricians and Gynecologists (ACOG) on his recent study, noted the following:

   "Women who use barrier methods who had been having sex with their partners for less than 4 months prior to getting pregnant had a 6.5-fold increased risk of getting preeclampsia, compared with women who did not use barrier methods and had been in a sexual relationship for more than 12 months." (26)

   Hence, the question arises: Why does a woman's body react as it does to seminal priming? Some researchers speculate that both the size of the human brain (compared to other mammals) and the amount of nutrient that is devoted to its development in the second and third trimesters (up to sixty percent) require "a second wave of implantation." (27) It seems that "[t]he large size of the human fetal brain requires deep endovascular trophoblast invasion," (28) which constitutes the second and more involved implantation not found in other mammals. Prior exposure to the same male antigens found in the embryo is critical to the success of this second phase of implantation: "[H]umans are the only species to undergo a second phase of implantation, there may be a critical period of prenatal development in which the presence of the father's semen facilitates the second phase of implantation." (29) In sum, "[e]xposure to paternal alloantigen occurs in two waves in the reproductive process--initially during transmission of seminal fluid at coitus, and secondly when placental trophoblast cells invade maternal tissues during embryo implantation." (30) In other words, paternal antigens are presented to the woman's immune system in two procreative waves: first, by the semen and second, by the embryo itself, should fertilization occur.

   Although the complete etiology of preeclampsia still remains largely a mystery to the medical community, immunologists are certain that seminal fluid priming significantly improves the odds of avoiding this disease. (31) This working hypothesis is corroborated by evidence that a previous pregnancy fathered by the same man reduces the rate of preeclampsia. (32) In this way, a previous normal pregnancy provides protection against preeclampsia, (33) provided that the second pregnancy is fathered by the same man who fathered the first. (34) This holds true even when the first...