In approximately half the couples with recurrent pregnancy loss (RPL) the tests will all come back normal. These include tests for checking the uterine cavity (hysterosalpingogram, sonohysterogram, or hysteroscopy), hormonal tests, parental chromosomes, autoimmune tests and (in selected cases) a thrombophilia panel. What next?
Often, we will advise the couple to try again and to call us with a missed period. Early pregnancy monitoring is an excellent way of providing supportive care. This includes two measurements of hCG levels and positive feedback at every opportunity.
We will often check a progesterone level and if it is less than 15 ng/mL, we prescribe vaginal progesterone (usually Crinone 8% once every morning until 11 gestational weeks). Early ultrasonography examinations are scheduled and continued weekly until the pregnancy has progressed beyond the point of the patient’s prior losses. It is important to continue with regular emotional support in these patients.
There have been at least three large trials confirming that this strategy results in a successful delivery rate of about 70% to 80%. If there is another loss in a patient with previous RPL and with the second early miscarriage, we recommend a chromosomal analysis (karyotype) on the products of conception. If the karyotype is abnormal, this knowledge helps the couple come to terms with the loss and may help avoid unproven therapies. If the karyotype is normal and a full investigation using evidence-based diagnostic tests for definite or probable causes of RPL is negative, we encourage the couple to wait at least 2 months and then try again for a successful pregnancy.
The use of heparin in patients with normal autoimmune tests has been evaluated and did not show any improvement in outcomes. Its use in this situation is not recommended.
The role of in vitro fertilization with preimplantation genetic screening (PGS) of embryos remains unclear. This makes sense because in younger patients with RPL the products of conception are abnormal in only 35% of cases. So PGS will be expected to be of limited use. Patients greater than 38 years of age will often produce few eggs. In this situation, the success rate with PGS is generally quite low, once again limiting its usefulness.
In rare patients with unexplained RPL, the use of in vitro fertilization with transfer of the embryos in a host uterus (gestational surrogacy) may be considered.