Cytokines and Pentraxin 3 Levels in Unexplained Recurrent Pregnancy Loss: Role of Oral Micronized Progesterone Therapy as Immunomodulator on Their Levels and Pregnancy Outcome, a Prospective Comparative Study

To assess cytokines(TNFα, IL6) and pentraxin3(PTX3) in unexplained recurrent pregnancy loss(RPL) compared to controls and to evaluate immunomodulatory effect of oral micronized progesterone.

This prospective comparative trial was conducted in 90 pregnant females: 60 RPL(group-1) and 30 controls(group-2). Group-1 was randomized into group-1a (n = 30) receiving oral micronized progesterone 200 mg twice daily and group-1b (n = 30) not receiving progesterone. TNFα(Th1-cytokine), IL6(Th2-cytokine) and PTX3 were measured at baseline(< 8 weeks), 16 weeks and at abortion/delivery.

In all three groups, baseline TNFα, IL6 and PTX3 were similar; and levels increased as pregnancy advanced. However, progesterone modulated the rise favorably in group-1a, which was similar to controls (group-2). A significant rise at 16 weeks was noted for TNFα in group-1b (p = 0.0002); IL6 in group-1a (p = 0.0001) and group-2 (p = 0.04); and PTx3 in group-1b (p = 0.028); number of previous abortions not affecting rise. The abortion rate was 3.5% vs. 16.7% in group-1a and 1b, respectively. No patient aborted if baseline TNFα was < 6.5 pg/ml and PTx3 was < 3441 pg/ml.

Favorable shift in TNFα, IL6 and PTx3 levels with oral micronized progesterone appears to exert immunomodulatory effect that support pregnancy continuation in RPL. Baseline TNFα < 6.5 pg/ml and PTx3 < 3441 pg/ml have good pregnancy outcome even without progesterone support. Women with higher levels than these can be offered progesterone therapy.

Trial registration

Clinical trial registry of India (CTRI/2016/09/007278).