Dr Ole Christiansen, a consultant registrar at the Rigshospitalet Fertility Clinic in Copenhagen, Denmark, told the annual conference of the European Society of Human Reproduction and Embryology, that giving birth to a boy first was not only a risk factor for subsequent miscarriages, but for women who suffered unexplained secondary recurrent miscarriages (SRM) it could mean that they never managed to carry a child to full term again unless doctors gave them appropriate treatments.
Dr Christiansen said: "Giving birth to a son is known already to be a prognostically negative factor in many obstetrical complications. Therefore we wanted to assess the impact of the gender of the first child on the outcome of subsequent pregnancies among patients with unexplained secondary recurrent miscarriages."
He studied 204 SRM patients admitted to clinics between 1986 and 2000, and obtained information on subsequent pregnancy outcome in 181 patients admitted before 2000. Among the patients admitted before 2000, only 54.4% of those who gave birth to a boy in their first pregnancy had given birth to a second live baby by January 2002, compared with 73% of women whose first child was a girl.
Amongst a subset of women who did manage to have a second child after a series of miscarriages, those whose first child was a boy had an average of 3.9 miscarriages before achieving a second birth, while women whose first child was girl had 3.5 miscarriages before delivery of a second child - a small but statistically significant difference. Average birth weights of the second children tended to be 181g higher where the first-born was a girl.
Dr Christiansen said: "Our study shows that the majority (54.4%) of those who gave birth to a boy in their first pregnancy go on to have a second child. However this percentage is lower than for those who gave birth to a girl first. Among my patients I have at least 50 who never have a second child after the first birth of a boy, whereas approximately 20 patients did not experience another birth after having a girl. So there are patients who will never get a second child in both groups, but the risk is larger among women whose first child was a boy."
He believes that the way women's immune systems react to male foetuses is the explanation for his finding and that therefore it will be possible to treat successfully women who suffer from SRMs. "These women may have raised an immunological reaction against tissue types that are expressed on the surface of the placenta in pregnancies with boys," he said. "The placenta is created from the foetus and if it is a boy it will carry these male-specific tissue types. The mother's immune system may be reacting by forming antibodies, but also the mother's white blood cells may be reacting against the placenta."
The first pregnancy is able to proceed to full term because the pregnancy is safely established by the time the mother's immune system starts to react to the male foetus. However, it is possible that the immune systems remains activated after delivery and affects subsequent pregnancies, believes Dr Christiansen.
"This is an epidemiological study, so we cannot be sure that such an immunological reaction is the explanation for our findings. However, no genetic disorder following the known rules of inheritance, can explain the findings. The impact of the gender of the first-born child on successive pregnancies is suggestive of something that has memory and only two tissues in the body are thought to have memory: the central nerve system and the immune system. Together with a PhD student, I have planned a series of genetic studies and immunological experiments to confirm or reject the theory of an impact of male specific antigens on the reproductive performance of women with SRM."
However Dr Christiansen believes his theory is probably correct because he has conducted two placebo-controlled trials in which infusions of intravenous immunoglobulin have been given to women with SRM to try to make their immune systems tolerate the male-specific antigens. This treatment increased the live birth rate by a factor of 2.3, whereas no effect could be detected in women who had never had a child and who suffered recurrent miscarriages.
"For many years it has been well-known that pregnancies with boys carry an increased risk for a long series of obstetrical complications compared with girl pregnancies. We believe that our research will be able to clarify whether these complications may be related to immunization against male-specific antigens. If this turns out to be the case, then I believe that we already have a quite efficient treatment, as our trials have shown."
Abstract no: O-163 (Tuesday, 15.45hrs CET, Paris room)
 SRM is defined as at least three consecutive miscarriages after a pregnancy that lasted more than 20 weeks.
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