Recurrent pregnancy loss

06Mar, 2023

Recurrent pregnancy loss (RPL)

1) What is RPL?

RPL is a condition characterized by two or more consecutive miscarriages. As a sporadic incidence,11-13% women miscarriage in their first pregnancy. The chances of repeat miscarriage after one, two and three spontaneous miscarriages, 14-21%, 24-29% and 31-33%. The recurrence risk increases as the gestational age at the time of loss increases.That means later in pregnancy the woman miscarries, the higher is the risk of a recurrence. Also, RPL typically occurs at a similar gestational age in consecutive pregnancies .

Miscarriage in all these contexts is defined as loss of pregnancy before the period of viability. ( Viability- The capacity of the foetus to survive outside the mother’s womb with appropriate support.) The period of viability differs in various countries. In India it is 28 weeks while in some countries it is 24 weeks.

2) What are the causes of RPL?

In over 40-50% cases, a cause may not be known despite all investigations. Abnormalities in the uterus- as arcuate or septate uterus, polyps, endometriosis are the uterine causes. Abnormalities in the chromosomes also can cause RPL. It could be that either of the parent is a carrier ( carries the gene but does not manifest the abnormality) of a chromosomal abnormality like a translocation which when transmitted to the foetus makes it impossible to survive and miscarriage is inevitable. Anti-phospholipid syndrome (APS) has a definite association with RPL though it is not as clear as with other immunologic factors and thrombophilias.

Environmental factors like exposure to heavy metals & pesticide, lack of micronutrients, longstanding infections of the uterus ( endometritis), inappropriate body mass, hormonal abnormalities like thyroid dysfunction, diabetes mellitus, hyper-prolactinemia have all been implicated as causes. There appears to be no association with caffeine intake. Smoking and alcohol may not have direct implications. Yet it is advisable to stop smoking and limit alcohol intake as it can impact pregnancy. It is also unclear if increased paternal age impacts pregnancy loss. It is unknown if stress causes or is the result of recurrent pregnancy loss.

3) What are the useful tests for evaluating a case of RPL?

The Poseidon Classification offers a guide to the possible approach to treatment.

  • • Evaluating the uterus for abnormalities. Of the various methods available, a 3D Ultrasound examination is the non-invasive test that can be used. 2D ultrasound along with Sonosalpingogram (SSG) may be useful if 3D ultrasound is not available. This modality is cheaper than MRI too. Hysterosalpingogram (HSG) can also detect uterine abnormalities. Hysteroscopy clinches the diagnosis in cases of septum or ppolyp and is also the best diagnostic and therapeutic procedure for the same
  •  Testing for APS- Anti- cardiolipin antidbodies, Lupus anti-coagulant are the important tests. Beta 2 glycoprotein can also be done
  • • Testing for Thyroid dyfunction, anti- TPO anti bodies, Diabetes mellitus and Hyperprolactinemia
  • • There appears to be nor role for routinely testing ovarian reserve,LH, Androgens or for Insulin resistance
  • • There appears to be nor role for routinely testing ovarian reserve,LH, Androgens or for Insulin resistance
  • • Testing for sperm antibodies or DFI 9 DNA fragmentation index) is routine not recommended

4) How is RPL treated?

The Poseidon Classification offers a guide to the possible approach to treatment.

  • • Tender , Loving care- Many couple conceive while on treatment because the stress levels are reduced
  • • Therapeutic intervention is guided by the underlying cause
  • • Uterine abnormalities are best treated by hysteroscopic resection. Cervical encirclage is not indicated in women with no history suggestive of cervical incompetence.
  • • For chromosomal factors, treatment may include IVF with PGD (pre-implantation genetic testing of the embryo) before euploid embryo transfer, pre-natal testing by chorionic villus sampling or amniocentesis and termination of pregnancy if the fetal abnormality is too severe to be correctable.
  • • For women who test positive for APS, aspirin with heparin therapy is indicated as it improves live pregnancy rates. Correction of thrombophilia with anti-coagulant therapy does not reduce RPL though it prevents maternal complications like deep vein thrombosis.
  • • Correction of thyroid abnormalities, hyperprolactinemia and diabetes is indicated.
  • • Effectiveness of Metformin in PCOS to reduce recurrent pregnancy loss is not proven
  • • Treatment options for Unexplained RPL include lifestyle modifications, Luteal phase progesterone, use of hMG ( Human menopausal Gonadotrophin) for ovulation induction , IVF with PGD, oocyte donation and surrogacy.
  • • Unproven therapies in unexplained RPL include using Clomiphene citrate for ovulation induction, Aspirin with or without heparin, steroids, IvIg ( Intravenous Immunoglobulins)
  • • Future therapies include use of Sitagliptin (inhibitor of dipeptidyl-peptidase IV) as it has shown improved endometrial mesenchymal stem-like progenitor cell (eMSC) colony counts. Another therapy- Granulocyte colony stimulating factor (G-CSF) has also shown promising results. However, adequately powered clinical trial data are needed

To Conclude,

Recurrent pregnancy loss is traumatic to the couple and a challenge to the treating physician. Every case needs to be evaluated separately and the investigations must be directed towards the suspected cause. The treatment is also tailor made to every patient and the causation. In all cases extreme empathy and tenderness while dealing is mandatory.

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