For patients with recurrent pregnancy loss
The progesterone level (P) was measured between 5 and 9 days of elevated temperature, and luteal dysfunction (P<10ng/ml) was diagnosed in 23.4% of the patients examined (22). However, when the next miscarriage rate was examined in the presence or absence of luteal dysfunction, it was found to be similar in both normal and abnormal groups (22). Luteal function varies from cycle to cycle, so it is difficult to assess this factor alone.
A randomized control trial was conducted to examine the role of progesterone in recurrent miscarriage (PROMISE). The trial was undertaken at 36 sites in the UK and 9 sites in the Netherlands to determine the effect of progesterone vaginal suppositories on 1568 patients with unexplained recurrent miscarriage (23). Of these, 836 patients became pregnant within one year, with 65.8% (262/398) in the progesterone group and 63.3% (271/428) in the placebo group having live births with no significant improvement as a result of the treatment. There were no significant differences in the rates of miscarriage (32.2, 33.4), stillbirth (0.3, 0.5), preterm birth (10.3, 9.2), congenital anomalies (3.0, 4.0), and genitourinary congenital anomalies (0.4, 0.4) between the two groups. There was no increase in congenital anomalies, including those affecting genitourinary and reproductive systems, as had been feared, but there was also no improvement in the birth rate.
However, the same group then looked at the effect of progesterone vaginal suppositories on 453 women who experienced bleeding in early pregnancy and found that 75% (1513/2025) of the progesterone group and 72% (1459/2013) of the placebo group gave birth, a trend that showed improvement, but not to any significant degree (23).
Prolactin is a hormone that is active in the production of milk. It is also secreted by the brain in the absence of fertility and it is known that hyperprolactinemia can cause ovulation problems and is associated with infertility. It is not yet clear whether hyperprolactinemia causes habitual miscarriage. One report suggests that bromocriptine for up to 9 weeks' gestation may improve the success rate, but this has not been followed up.
Diabetes mellitus and hypothyroidism are established causes of miscarriage. Because diabetes is diagnosed in only about 1% of RPL cases, there has been a lack of quality research. Subclinical hypothyroidism occurs in about 15% of cases, but the need for treatment is not yet clear (25). In addition, it has recently been found that treatment has no benefit in patients who are positive for anti-TPO antibody, a thyroid-associated autoantibody (26).
A relationship between miscarriage and an endocrine disorder known as polycystic ovarian syndrome (PCOS) and miscarriage has been reported. It is diagnosed by a long menstrual cycle and characteristic findings in the ovaries as seen by ultrasound. Since it occurs in about 5% of patients with RPL and is often associated with diabetes mellitus, hypothyroidism, and hyperprolactinemia, we considered the possibility that these form one group of diseases. However, the means of prevention of miscarriage in patients with PCOS have not yet been established.
- Definition of recurrent miscarriage and recurrent pregnancy loss and results of the Japan Environment and Children’s Study (JECS)
- Examination and causes of RPL
- Antiphospholipid syndrome
- Treatment of antiphospholipid syndrome
- Chromosomal translocation in either partner
- Preimplantation genetic testing for chromosomal structural rearrangement
- Congenital uterine anomaly
- Thrombotic predisposition
- Endocrine abnormality
- Fetal or embryonic aneuploidy
- Preimplantation genetic testing for aneuploidy
- Immunotherapy for unexplained recurrent miscarriage
- Drug administration for repeated miscarriages of unknown cause
- Unknown Causes
- Emotional support