Benefits of Vaginal Micronized Progesterone at Start of Luteal Phase in Recurrent Pregnancy Loss

17 Aug, 21

Introduction

There are various factors contributing to recurrent pregnancy loss (RPL), one of them being endometrial factors. An endometrial molecular marker nuclear cyclin E (nCyclinE) was found to be associated with a history of infertility and a possible marker of endometrial development. Progesterone supplementation is usually initiated shortly after LH surge to improve the endometrial development in assisted reproductive techniques. There is abnormal increase in the levels of nCyclinE in the luteal phase in women with a history of RPL of <10 weeks.

Aim

This study evaluated if the pregnancy outcomes improve with supplementation of vaginal micronized progesterone (P) beginning 3 days after LH surge in women with RPL.

Method

Study Design

Observational cohort study.

Treatment Strategy

The cohort comprised women with a history of two or more unexplained pregnancy losses <10 weeks in size, who underwent endometrial biopsy (EB) performed 9-11 days after LH surge; and had at least 1 subsequent pregnancy.
Women with endometritis, maturation delay, or glandular-stromal dyssynchrony, and intraglandular neutrophils and macrophages were excluded.
In women with elevated nCyclinE (>20%), vaginal micronized P was prescribed at a dose of 100-200 mg every 12 hours starting 3 days after LH surge (luteal start).
Some women with normal nCyclinE (≤20%) also insisted on vaginal P given empirically at the same dose.
the control group included women with normal nCyclinE (≤20%) who did not receive P.

Endpoint

Ongoing pregnancy >10 weeks in size.

Results

Of the overall RPL cohort of 116 women; 51% (n = 59) had elevated nCyclinE and 49% (n = 57) had normal nCyclinE; out of which 43 women were given empiric P therapy.
there were no significant differences in maternal age body mass index, concomitant factors associated with RPL among the groups
Pregnancy success improved remarkably in the 59 women with elevated nCyclinE after treatment with vaginal P: 6% (16/255) in prior pregnancies versus 69% (57/83) in subsequent pregnancies.
Among women with normal nCyclinE levels, the difference in pregnancy rate between those on empiric treatment of vaginal P and those without was insignificant (67% vs 51%; p=0.14)
Pregnancy success rate in subsequent pregnancies was significantly higher in women prescribed vaginal micronized P compared with controls: 68% (86/126) versus 51% (19/37); odds ratio = 2.1 as seen in Figure 1.

Figure 1. Pregnancy success rate

Conclusion

Administration of vaginal micronized progesterone at the start of luteal phase improved the pregnancy success rates in a strictly defined cohort of women with recurrent pregnancy loss (RPL).
The authors of this study recommend molecular analysis of luteal phase endometrium to identify the women who can be benefitted the most with vaginal progesterone given from the start of the luteal phase.

Fertil Steril. 2017 Mar;107(3):684-690.e2. Doi: 10.1016/j.fertnstert.2016.11.029.