Reproductive immunology is the medical specialty that deals with the study of disorders related to immunity and gestation. Pregnancy is a physiological state in which maternal cells and antibodies modulate the immune response to the embryo, thus facilitating its implantation and development. When a dysfunction or imbalance occurs in this tolerance system, pre-embryonic (recurrent implantation failures, repeated early miscarriages), embryonic (first trimester miscarriages) or fetal (second or third trimester fetal deaths) problems occur, as well as placental involvement (pre-eclampsia, intrauterine growth retardation and/or prematurity).
In which cases should reproductive immunology be used?
Reproductive immunology should be resorted to, in the case of patients affected by the following:
- Repeated miscarriages
- Fetal losses
- Prematurity
- Recurrent implantation failure (unsuccessful IVF)
- Placental pathology (pre-eclampsia, intrauterine growth retardation, abruptio placentae, placental abruption and placental hematoma).
- Maternal clinical conditions during pregnancy (thrombosis, reticular lividity, chorea or neurological disorders).
- Analytical alterations in the mother during pregnancy (low platelets, hemolytic anemia, coagulation disorders), as well as fetal disorders (low birth weight and bradycardia).
What benefits does reproductive immunology bring to the patient?
It involves a holistic approach to the patient’s immune status, improving the prognosis for the current pregnancy or new pregnancies. An immunological profile is designed according to the results obtained in the study, carrying out the pertinent modifications in treatments or lifestyle habits. If a good diagnosis is made and we stratify the risk by adapting the treatment, the success rate ranges between 70 and 85%. Treatment is initiated before the new gestation, and is usually withdrawn in the late puerperium.
Disadvantages and risks of reproductive immunology
In all cases, the diagnostic approach involves blood tests, with no measurable risk. Depending on the results, treatments are administered which, as a general rule, do not present maternal or fetal risks beyond the intrinsic risk of each drug, independently of the pregnancy. There are no major inconveniences other than having to periodically administer a treatment to improve the success rate of a future pregnancy.
What is the relationship between reproductive immunology and recurrent miscarriages?
Recurrent abortion (RA) groups together those cases with a history of 3 or more than 3 consecutive first trimester abortions. In certain situations, cases with 3 non-consecutive miscarriages and exceptionally, cases with 2 consecutive miscarriages can also be included under this heading. It is important, if possible, to know if an embryo was present in these abortions and if the presence of a fetal heartbeat was documented.
Miscarriage affects up to 15% of couples of childbearing age. About 5% will have 2 and 2-3% of cases will have three or more miscarriages. Fetal loss is understood to be that which occurs after the 10th-12th week of gestation. If this accident occurs beyond the 20th week, we speak of fetal death.
Immune-related miscarriages can have an autoimmune or alloimmune cause. Alloimmune miscarriage occurs when the mother’s immunological tolerance mechanisms against paternal anti-hygienic determinants do not work properly. There is a rejection of the part of the embryo that comes from the paternal genetic material. These are usually first trimester abortions. On the other hand, an autoimmune miscarriage is caused by the maternal loss of immunological tolerance against her own cells, against certain autoantigens. This error in the recognition of one’s own causes inflammatory alterations in various parts of the body, including blood vessels and placenta.
What is recurrent implantation failure syndrome?
It is those cases in which pregnancy is not achieved after a minimum of two transfers with a minimum of 2-3 total viable embryos. Although the exact causes are unknown, there is a possibility that inflammatory and/or autoimmune disorders play a role beyond chromosomal causes. Appropriate study could perhaps provide a possible solution to these cases.
What are the most frequent obstetric complications in women with antiphospholipid antibodies?
Antiphospholipid antibodies (aFL) are a paradigmatic example of specific autoimmunity. These antibodies can cause inflammation first of the blood vessels and then of the placental cells -trophoblasts-, eventually leading to miscarriage. The most frequent obstetric complications associated with these antibodies are:
- Recurrent miscarriage
- Fetal loss
- Fetal abortion
- Prematurity
- Pre-eclampsia
- HELLP syndrome
- Eclampsia
- Intrauterine growth retardation
- Retroplacental hematoma
- Placental abruption (abruptio)
- Recurrent implantation failure
Are there studies that facilitate the understanding of reproductive problems?
Yes, these types of studies do exist. They are not conventional analyses that can be performed in any laboratory, but many isotype autoantibodies, degrees of maternal-paternal compatibility, expression of certain risk genes and haplotypes can be studied, as well as cells and cellular subtypes that can predict possible disease or the probability of a high risk of suffering new negative events.
Fortunately, the answer is yes. If we make a good diagnosis and stratify the risk by appropriate treatment, the success rate ranges, depending on the exact cause, from 65 to 80% of cases. Treatment is initiated before the new gestation, and is usually withdrawn during pregnancy or in the late puerperium in cases of autoimmune problems.
In conclusion, it can be stated that even if good embryos are available, if they do not find an adequate environment, implantation or placentation will not prosper. The use of classic treatments, but which can act by different mechanisms already known today, and other new ones such as: TNFα inhibitors, IVIGs, drugs that increase maternal tolerance to paternal-dependent fetal antigens, filgrastim, lenograstim, phosphodiesterase inhibitors, cyclophilin inhibitors, and others alone or in combination, can drastically change the reproductive prognosis of these couples. Currently, other drugs are already being investigated with positive results.