Pregnancy Outcome After Secondary Recurrent Pregnancy Loss (sRPL) is Influenced by Sex of the First Born Child and Maternal Carriage of HY-restricting HLA Class II Alleles

In a Danish cohort (Kolte et al., 2016, Nielsen et al., 2009) the first pregnancy outcome after admission and the long term live birth rate were associated with carriage of known HY-r HLA class II alleles in the sRPL patient with a first born boy, but not in the sRPL with a first born girl. The live birth rate in the first pregnancy after admission and the hazard ratio for live birth on longterm were comparable between sRPL with a first born girl and boy if the sRPL did not carry a HY-r HLA class II allele. In contrast, sRPL after a first born boy had a significant poorer prognosis than sRPL after a first born girl when the patients carried ≥1 HY-r HLA class II allele.

These findings were the first of its kind and it has not been confirmed in other cohorts ever since. In a new Danish cohort from another region of Denmark, this study will examine if these findings can be replicated.

Before data collection, a sample size calculation was performed based on the findings in the former studies (Nielsen et al., 2009; Kolte et al., 2016). These studies differ from the present study, since Nielsen et al. (2009) included HLA DRB3*0301 but not HLA DRB1*07 as a HY-r allele, and Kolte et al.(2016) included HLA DRB3*0301 too and measured the cumulative live birth rate in contrast to first pregnancy outcome measured in the present study. However, the sample size calculation based on weighted calculations on results from these studies is the closest we get a suitable sample size for the present study. The sample size in the present study should consist of at least 88 sRPL patients with a first born boy with maternal HY-r HLA class II allele and 73 sRPL patients with a firstborn boy and no maternal HY-r HLA class II alleles on weighted calculations with an alpha level = 0.05, a power of 80 %, and a inclusion ratio of 1.2 more with than without such HLA carriage. The sample size needed to find difference between women with a firstborn boy vs girl with such HLA carriage was smaller; ie. 48 patients for comparing patients with ≥1 HY-r HLA alleles. As this was the primary aim, this sample size was considered sufficient for the study.

Study inclusion started January 1, 2016, and will end when this sample size is reached.

The anticipated sample size of the pRPL group is 1.2 times the total number of sRPL patients since pRPL normally account for about 55 % of RPL patients. Thus, 180 patients are expected in the pRPL, although this is not taking into account when deciding the timing for final follow-up and data collection.