Spontaneous pregnancy loss is a common occurrence, with approximately 15% of all clinically recognised pregnancies resulting in pregnancy failure. Recurrent pregnancy loss (RPL) is defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period. It affects approximately 1% to 2% of women.
At present, accepted causes of RPL include parental chromosomal abnormalities, untreated hypothyroidism, uncontrolled diabetes mellitus, certain uterine anatomic abnormalities and antiphospholipid antibody syndrome (APS). Other probable or possible causes include endocrine disorders, heritable or acquired thrombophilias, immunologic abnormalities, infections, and environmental factors. After evaluation for these cases, approximately half of all cases still remain unexplained.
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Causes Suggested Diagnostic Evaluation
Genetic Possible testing for parental karyotype
Anatomic Hysterosalpingogram (HSG) or office hysteroscopy, 2D or 3D ultrasound saline infusion hysterography
Endocrine Measurement of thyroid stimulating hormone, serum prolactin, ovarian reserve; possible testing for insulin resistance, antithyroid antibodies Infectious No evaluation recommended unless the guest has evidence of chronic endometritis/cervicitis on examination, or is immunocompromised Autoimmune Possible testing for lupus anticoagulants, anticardiolipin antibodies (IgG and IgM)
Non-APS thrombophilias Possible testing for homocysteine, factor V Leiden, prothrombin promoter mutation, activated protein C resistance
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Therapy should be directed towards treatable causes and may include in vitro fertilisation with preimplantation genetic diagnosis, use of donor gametes, surgical correction of anatomic abnormalities, correction of endocrine disorders, and anti-coagulation or folic acid supplementation. For women with unexplained RPL, progesterone is noted to be beneficial in reducing miscarriage rates. In addition, low-dose aspirin has presented benefits for those with a history of losses at more than 13 weeks of gestation.
This case is about a couple who began consulting me in 2012, and whose treatment lasted 5 years. The wife, whom we shall call Mrs X, was 30 years old at the time and had a history of three spontaneous abortions. All three pregnancies, she had conceived naturally. After their third miscarriage, the couple had been unable to conceive again. When they came to me just over two years later, I performed a thorough evaluation and found that the reports were normal. I recommended intrauterine insemination (IUI) as a first-line treatment, and Mrs X conceived in the first cycle, only to lose the pregnancy at 3 months. After 2 more unsuccessful IUI cycles, I advised the couple to consider intracytoplasmic sperm injection (ICSI).
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I performed Mrs X's first cycle of ICSI with Provision - a technology for real-time imaging of embryos that aids in embryo selection. She conceived, but once again, had a miscarriage in her 5th month of pregnancy. At this stage, I suggested using an advanced technology called preimplantation genetic screening (PGS), where embryos are biopsied and sent for genetic evaluation, and a chromosomally viable embryo is selected for transfer. The PGS procedure proved successful, but sadly, Mrs X experienced yet another miscarriage at 3 months. Still optimistic, we tried two more frozen embryo transfer cycles. These, however, were also unsuccessful. It must be noted that on all the cycles administered, Mrs X was on anticoagulants, as per the standard embryo transfer guidelines.
After these attempts, the couple decided to take a break. When they returned to me the following year, I recommended oocyte donation and surrogacy. However, they had their heart set on another in vitro fertilisation (IVF) cycle; this time, without PGS. Given their history, it was a tough call and I tried to discourage Mr and Mrs X against another attempt. However, they were persistent, and after pursuing a fresh round of ICSI, they conceived. Like all the previous times, Mrs X was administered anticoagulants. Yet, this time, she sailed through her entire pregnancy without any issues. She delivered a healthy baby girl at full term. Needless to say, Mr and Mrs X's pregnancy was a happy surprise, as the couple had experienced 6 prior miscarriages despite genetically normal embryos.
The prognosis for a couple with RPL depends entirely on the underlying cause of pregnancy loss and the number of prior losses. Couples should be encouraged and counselled about their overall prognosis, given that even after 4 consecutive losses, a woman has more than a 60% to 65% chance of carrying her next pregnancy to term. This particular case is one such, where the couple successfully beat the odds and delivered a child despite 6 prior miscarriages.
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