Recurrent
pregnancy loss (RPL) is one of the most traumatic and frustrating experience
for patients and consulting obstetricians. It is an area of obstetrics lacking in
evidence based diagnostic and treatment strategies. As per data by American Society
for Reproductive Medicine(ASRM) it affects 15-25% of all pregnancies and in
nearly 50% of cases the cause is not known.
Therapeutic interventions
are generally based on the cause of RPL and data from observational studies and
clinical experiences of the treating obstetrician. Treatment options range from
active interventions in the form of hormonal supplementation to masterly
inactivity (= reassurance).[i]
Progesterone
(P) has long been used in the treatment of infertility because of its immunomodulator action
on endometrium but it’s use is largely empirical along with other treatment regimen.
Cochrane review and meta-analysis concluded
that P supplementation could improve the reproductive outcome in women with 3
or more pregnancy loss.
But, in none
of these studies P was started after LH surge (luteal start) and varied route
and dosing of P administration was used. [ii]
A new study
published on line on January 9, 2017 in Fertility & Sterility international
journal of the American Society for Reproductive Medicine assessed the
effectiveness of luteal start vaginal micronized P in a recurrent pregnancy
loss (RPL) cohort.
In this
observational, cohort study 116 women with a history of RPL were recruited and
followed prospectively. Vaginal micronized progesterone was supplemented in dose
of 100–200 mg every 12 hours starting 3 days after LH surge
(luteal start corresponding to day 13 of the cycle) with or without >20%
increase in levels of nuclear cyclin E (nCyclinE) expression. The controls did
not receive P and had normal nCyclinE (≤20%). P was continued till 10
weeks of pregnancy.
The research
team lead by Dr. Mary D. Stephenson tested Nuclear cyclin E (nCyclinE) levels
to assess the state of endometrium. It is an endometrial molecular marker(EFT)
and a cell cycle regulator, levels more than 20% after day 20 of the menstrual cycle
correlates with a history of infertility. NCyclinE expression was determined by
an EB was performed 9–11 days after the LH surge in previous cycle.
Of 116 women
tested, 59 had high levels of nCyclinE and 57 had normal levels.
The results
of the test were very promising with 68% pregnancy rate in study group as
compared to women who did not take P. The chances of successful pregnancy increased
from 6% to 69% in treatment group.
Six women
needs to be treated with P to achieve one additional successful pregnancy.( Number need to treat).
This
observational study cannot establish causality, the researchers believe that P
is beneficial in changing the endometrial milieu and benefitting the developing
embryo.
Dr.
Stephenson said “The positive results show us that next we need to study
progesterone as a treatment for recurrent pregnancy loss with a prospective
randomized trial to validate the findings."
[i] http://blog.drmalpani.com/2016/08/pgs-for-recurrent-pregnancy-loss-forget.html
[ii] Haas,
M.D. and Ramsey, P.S.
Progestogen for preventing miscarriage. Cochrane
Database Syst Rev. 2013;: CD003511
