A study done previously by a Danish recurrent miscarriage clinic observed patients referred from 1986 to 1999 and found that firstborn boys opposed to firstborn girls are far more frequent in mothers with secondary recurrent miscarriage. Also, a firstborn boy was correlated to a less favorable pregnancy potential. In the 14-year follow-up done by the clinic, mothers with firstborn sons had fewer subsequent live births than mothers with firstborn daughters.

Approximately 1% of women have what is known as recurrent miscarriage. This means that they have had at least 3 consecutive miscarriages. Of that 1%, approximately 1/3 suffers from secondary recurrent miscarriage, meaning that they have had a child prior to having repeated failed pregnancies.

Why would male fetuses cause miscarriage?

To explain the study results, researchers came up with a hypothesis stating that a mothers’ immunization against male HY antigens during the first pregnancy is responsible for the further miscarriages. Only male fetuses produce these HY antigens. They are part of the reason a male develops into a male in the uterus during gestation. During a pregnancy with a male fetus, HY antigens are produced by the fetus and eventually make their way into the mother’s circulation. The mother’s immune system, recognizing these proteins as foreign, will start to produce antibodies against the HY antigens. Later on in other pregnancies, the lingering immunity could cause the mother’s body to reject the fetus. This immunity has been demonstrated up to 22 years after the birth of a boy.

New Miscarriage Study

To confirm or deny the hypothesis that having a firstborn son has a negative effect on women with secondary recurrent miscarriage, researchers decided to look at a new group of patients. The results were combined and compared to those of the previous study done from 1986-1999.

Women included in the study had to have had a previous pregnancy lasting for at least 22 weeks before the series of miscarriages to be considered a patient with secondary recurrent miscarriage.

Miscarriage Study Methods

Patients were divided into two groups. The first group of 175 patients was taken from the previous study from 1986 –1999. The second group was composed of 130 patients referred from 2000 –2005. Pregnancy and miscarriage information was obtained from all patients.

Miscarriage Study Results

The combined results showed that among women with secondary recurrent miscarriage, 60.3% of the women had firstborn boys compared to 39.7% which had firstborn girls. This is very different from the normal Danish population which generally has 51.8% firstborn males to 48.2% firstborn females.

Accordingly, the odds for a live birth in a patient with secondary recurrent miscarriage with a firstborn boy are only 0.37 of that of a patient with a firstborn girl. For additional miscarriages, the odds for a live birth are reduced by 39% each time.

Most miscarriages are due to fetuses having an abnormal number of chromosomes. An interesting observation in this study is that while only 14 of the 83 miscarriages could successfully have their chromosomes analyzed, all 14 had normal chromosomes. This means that the most common reason for miscarriage was not present in these pregnancies. On the other hand, the ratio of male to female fetuses was equal.

Discussion

The current study seems to confirm the results of the initial Danish analysis. In women with secondary recurrent miscarriage, there are many more that have firstborn sons opposed to firstborn daughters. Furthermore, the firstborn sons had a negative impact on the chance of a subsequent live birth in each group of women studied.

As previously stated, the mothers’ immunity to the male HY antigens is the researcher’s primary hypothesis as to why more firstborn boys are born to women with subsequent secondary recurrent miscarriage than firstborn girls. The results showed that both sexes of fetuses were miscarried. However, the ratio of boys to girls in the live born babies was lower than expected. The normal Danish ratio is 107 boys to 100 girls. In this study, there were only 85 bos to every 100 girls, this may indicate that male fetuses are being lost more frequently.

Conclusion

To date, evidence that these HY antigens play a role in secondary recurrent miscarriage is only observational. Nevertheless, the data shows that firstborn males have a much larger negative impact in women with secondary recurrent miscarriage than firstborn females. Women with this condition and a firstborn male are less likely to have success in having a live birth.

Is there a treatment for this type of miscarriage?

This condition leaves many women frustrated and discouraged. Some of the patients at this center were treated with IVIG or Intravenous Immunoglobulin. IVIG is a blood product administered in the veins that contains important antibodies used by the immune system. It was hoped that IVIG may reduce the mother’s immune response and lessen the chance for loss. Studies of IVIG in couple with recurrent loss have had mixed results and thus it is considered experimental only. Another possible option to treat these couples is to attempt pregnancy with IVF combined with PGD. PGD can be used to select for female embryos only. Since female embryos lack the HY antigen, the mother’s immune system should theoretically not reject a female fetus.