Modulation of the cardiovascular and immunologic characteristics by aerobic exercise in women with recurrent miscarriage

Recurrent miscarriage is defined as 2 or more spontaneous miscarriages, with a
gestational age under 16 weeks. The incidence of recurrent miscarriages in the
Netherlands is around 3% in women of fertile age. In very early gestation
embryonal factors are more often involved, while spontaneous miscarriage after
6 weeks gestation more often involve maternal factors.
The exact etiology of recurrent miscarriage can only me found in less than 50%
percent of the patients. Uptill now known maternal factors are: thrombophilia,
auto-immune disease, uterus anomalies and hyperhomocysteinaemia. Furthermore
women with recurrent miscarriage have an increased resistance in the uterine
artery. The latter observation suggests abnormal haemodynamic functioning;
which is likely to be associated with the increased risk of preeclampsia in
women with recurrent miscarriage in a next (ongoing) pregnancy. Also, both
women with a history of preeclampsia as women with a history of recurrent
miscarriage haven an increased life-time risk of cardiovascular disease.
Furthermore, women with recurrent miscarriages often have immunologic
abnormalities, characterized by increased T-cel activation and disbalance
between regulatory and cytotoxic "natural killer cells". This immunologic
disbalance is likely one of the negative factors involved in reproductive
failure.
It is known that exercise has a possitive effect on pregnancy and the
riskprofile associated with cardiovascular disease and the immune systeme.
Possibly also women with recurrent miscarriage can improve their haemodynamic
functioning by physical exercise; it would be an advantage if this would
improve the cardiovascular adjustment and a more beneficial immune response to
the early pregnancy. Plasma volume expansion is an important factor in this
adjustment. Therefore, in this pilot study, we would like to study the effects
of one month training on the haemodynamic functioning and the immune profile in
women with recurrent miscarriage.

To study the effects of physical training on vascular, endothelial and
immunologic functioning in women with recurrent miscarriage; results are
compared with women who have never been pregnant (nulligravid controls) and
women who have a history of an uncomplicated pregnancy (primiparous controls)

Prospective intervention study

The burden associated with participation is mainly the time intensive aspect of
the study. Participants have a 4 weeks training programm with cardiovascular
evaluation befor and after training. The training itself is not associated with
any known risks.

Participants will be asked to have a constant sodium intake in the advance week
of measurement, the total sodium intake is equal to the mean sodium intake.
Based on experience with this sodium constant diet, we know that the diet is
hardly considered to be any burden.

To determine plasma volue, labeled albumine delution method is used. The
nuclear medicine departmet is well known with this procedure. The radiation
exposure is minimal and is similar to the radiation exposure during a one-way
flight to Amsterdam- New York. The radiation exposure according "the
international commision on radiological protection (ICRP)" is categorie 1
("Trivial level of risk and minor level of social benefit required*).

During the study mostly non-invasive measurements of minimal burden are used to
measure cardiovascular functioning. Invasive procedure is minmised to the use
of two intravenous canulas. These canulas are used for bloodsampling and
determination of plasma volume after HSA I-125. During the study no medication
is used that is aimed to have health effects. Insufflation of the cuffs around
arm and leg is unpleasant. We are aware of the fact that there are women who
will experience discomfort with the transvaginal ultrasound measurement of the
doppler flow in the uterine artery. Because of the nature of this examination,
this measurement will take place at the department most familiar and
specialized with this technique.

In summary the burden and risk of participants is mainly considered to be time
extensive. Invasive aspect is minimal. On the other hand; there is likely to be
a positive health effect of physical exercise on physical and mental wellbeing.