More than eight and more than 12 miscarriages . With this very complex and desperate cover letter, many of the patients arrive at the Reproductive Immunology Unit of the San Carlos Clinical Hospital. A pioneering initiative in Spain that links two services: Clinical Immunology, headed by Dr. Silvia Sanchez-Ramon; and that of Assisted Reproduction, directed by doctor Ignatius Christopher.
They care for patients with implantation failures or recurrent pregnancy losses in which age is not a problem and for which no explanation can be found. «They come with harsh experiences. Very crushed and with a lot of psychological damage, but always with hope, “says Silvia Sánchez-Ramón. Most of them come from the Reproduction Unit of the Hospital. “Many times they are patients who come desperate with several pregnancy losses and who make us desperate because we get very good embryos in the laboratory and we achieve the pregnancy,” explains the gynecologist.
There are also highly informed patients who ask directly for Dr. Sánchez-Ramón and others referred from hospitals where they know about the existence of this pioneering unit. «The family doctor can make an appointment directly for the Reproduction Unit of our hospital because there is free choice. It is easy to get to us and not especially slow, “says Dr. Cristóbal.
Although all the cases that come to them are complicated, for Dr. Sánchez-Ramón those of women who have suffered late stillbirth (37-40 weeks of gestation) and sometimes repeatedly. “On many occasions they are inflammatory problems at the beginning of placentation. In these cases, we begin to treat with immunomodulation a month before they become pregnant”, explains the doctor.
The immune system is a recognition and response system and has to do with everything that happens in the body. In pregnancy it also plays its role. During pregnancy, the mother’s immune system must recognize the embryo and this recognition may have “a defective response”, in the words of the immunologist. When recurrent pregnancy losses or implantation failures occur, “in many cases it is due to excess inflammation and in others due to a lack of stimulation of the adequate immune system,” she points out.
Control the immune system
With pharmacological treatments, immunologists try to modulate that response and find the necessary balance so that everything goes well. “We use very low doses of drugs that have been proven to be very safe because the armamentarium of drugs in pregnancy is limited, but we are discovering more and more mechanisms. Twe have a very high success rate», says Silvia Sánchez-Ramón. Specifically, up to February 2022, 252 women have managed to have a child after receiving treatment in this unit, 94.2% of the patients. «That 6% that does not get it is where we have to investigate. There may be a mix of factors, not just immunological ones,” warns Dr. Cristóbal.
When women who have been studied and diagnosed by clinical immunologists get pregnant, either naturally or through assisted reproduction, the patients are closely followed by the hospital’s high-risk pregnancy consultation. In Reproductive Immunology they see them once a quarter to adjust the medication.
A novel discipline
Reproductive Immunology is a relatively recent discipline. It deals with a pathology that, until 15-20 years ago, remained in limbo: women with repeat miscarriages, fetal death, implantation failurepremature rupture of membranes… In short, obstetric problems without a clear explanation and that may be of immunological cause.
The Clinician’s Reproductive Immunology Unit was launched in 2019, with its own place on the Obstetrics floor, to fill a “gap” -in the words of Dr. Cristóbal- of all those patients who escape us due to ignorance of the inflammatory immunological mechanisms that exist in pregnancy. «As immunologists we are always consultants to other specialists. In this case, the obstetrician-gynecologist is the reference doctor”, says Silvia Sánchez-Ramón.
The idea of setting up a monographic service, with its own agenda, arose from the Immunology Unit, which had already seen Obstetrics patients since 2015. And Dr. Cristóbal gave them a space. “The most difficult thing in a hospital is to find space,” both say. Throughout Spain, there are 18 Clinical Immunology units in public hospitals, but only in the Clinic do they also have a unit focused on Reproduction.
Dr. Sánchez Ramón recalls the case of a patient with several fetal deaths in very late weeks that was sent to them from Galicia. “She finally had her baby and she wrote to me afterwards”, she recalls with a smile.
Ideally, this type of service would be available in all the autonomous communities, but both professionals acknowledge that it is not easy due to the lack of physical space in hospitals and the novelty of the discipline, which not all professionals are familiar with. “We are very interested in training people to help,” says Silvia Sánchez-Ramón.
more research
The immunologist believes that more research and more collaboration with obstetricians is still needed to continue establishing evidence-based guidelines. “I would love for us to get an inflammatory marker to know in advance if a pregnancy is going to go well or not,” says Dr. Ignacio Cristóbal as a wish for the future. Both are committed to the cause and convinced that they can help many more women .
“The immune system is exciting and you always have the feeling that there is a lot to learn. I like to see patients and also do research: go to the laboratory and study the parameters to see what you can do. Let’s go to the precision medicine», says the immunologist. “We work for the patients,” adds Dr. Cristóbal.
Some of these women even have repeated the experience of being mothers up to three times. “Once you have the pattern and it has worked, in subsequent pregnancies the process is faster,” they say.
And the day the delivery of these patients arrives, they can breathe. They are not births with greater risk for the mother or the baby, but the professionals are aware of the difficulties these women have had to reach that moment: “They are ‘golden children'”, says Ignacio Cristóbal.