Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss

Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss.

Volume 107, Issue 3, Pages 684–690


Mary D. Stephenson, M.D., M.Sc.,, Dana McQueen, M.D., M.A.S., Michelle Winter, M.D., Harvey J. Kliman, M.D., Ph.D.



To assess the effectiveness of luteal start vaginal micronized P in a recurrent pregnancy loss (RPL) cohort.


Observational cohort study using prospectively collected data.


Not applicable.


Women seen between 2004 and 2012 with a history of two or more unexplained pregnancy losses <10 weeks in size; endometrial biopsy (EB) performed 9–11 days after LH surge; and one or more subsequent pregnancy(ies). Women were excluded if concomitant findings, such as endometritis, maturation delay, or glandular-stromal dyssynchrony, were identified on EB.


Vaginal micronized P was prescribed at a dose of 100–200 mg every 12 hours starting 3 days after LH surge (luteal start) if glandular epithelial nuclear cyclin E (nCyclinE) expression was elevated (>20%) in endometrial glands or empirically despite normal nCyclinE (≤20%). Women with normal nCyclinE (≤20%) who did not receive P were used as controls.

Main Outcome Measure(s)

Pregnancy success was an ongoing pregnancy >10 weeks in size.


One hundred sixteen women met the inclusion criteria, of whom 51% (n = 59) had elevated nCyclinE and 49% (n = 57) had normal nCyclinE. Pregnancy success in the 59 women with elevated nCyclinE significantly improved after intervention: 6% (16/255) in prior pregnancies versus 69% (57/83) in subsequent pregnancies. Pregnancy success in subsequent pregnancies was higher in women prescribed vaginal micronized P compared with controls: 68% (86/126) versus 51% (19/37); odds ratio = 2.1 (95% confidence interval, 1.0–4.4).


In this study, we found that the use of luteal start vaginal micronized P was associated with improved pregnancy success in a strictly defined cohort of women with RPL.

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