Recurrent Pregnancy Loss and IVF


What is recurrent pregnancy loss (RPL)?

The American Society for Reproductive Medicine (ASRM) defines RPL as a condition when a woman has 2 or more clinical pregnancy losses (miscarriages) before the pregnancies reach 20 weeks. Biochemical losses are usually not included in making an RPL diagnosis, but some physicians do take these into account. Pregnancy loss is common, affecting up to 25% of pregnancies, but RPL is rarer, with less than 5% of people experiencing 2 consecutive miscarriages and less than 1% of people experiencing three or more losses. (1)

  • Clinical pregnancy is confirmed by an ultrasound conducted by a healthcare provider, or in the case of a miscarriage by examination of the products of conception.

  • Biochemical pregnancy loss is one that has been detected by urine pregnancy test or blood testing for hCG before then becoming negative.

What are some known causes of RPL?

  • Chromosome abnormalities in the embryo or fetus. A chromosomal abnormality (usually an abnormal number of chromosomes) is the most common cause of pregnancy loss, and the risk increases with advancing maternal age. The most common abnormality that is diagnosed is trisomy (one extra chromosome). Chromosomal abnormalities can be confirmed by genetic testing of the pregnancy tissue after a pregnancy loss. Sometimes, parents carry chromosomal alterations called ‘translocations’ that do not affect them personally but can lead to pregnancy loss due to an abnormal chromosome number in the embryo. These can be investigated via a parental karyotype, a blood test that examines parental chromosomes.

  • Antiphospholipid antibody syndrome is a syndrome associated with both early and late pregnancy loss, as well as other pregnancy complications. It is recommended that patients with greater than 3 unexplained pregnancy losses before 10 weeks, or one pregnancy loss after 10 weeks with no genetic abnormality should undergo evaluation via a blood test.

  • Shape of uterus (bicornuate, unicornuate, septum) or presence of fibroids, polyps or scar tissue in the uterus. Anatomic causes are more commonly associated with second trimester loss. These can be investigated by 3D ultrasound, saline infusion sonogram, hysterosalpingogram (an X-ray of the uterus), or hysteroscopy (a small camera inserted into the uterus through the vagina).

  • Untreated medical conditions (e.g., thyroid disease, diabetes). Well controlled diabetes is not a risk factor for pregnancy loss, but poorly controlled diabetes and other hormonal abnormalities (high or low thyroid function, high prolactin levels) are associated with pregnancy loss.

  • A healthy lifestyle is recommended for anyone trying to conceive. Smoking tobacco, drinking alcohol (>3-5 drinks/week), and cocaine use have all been associated with an increased risk of miscarriage.

When would IVF be indicated?

  • IVF may be recommended for RPL due to genetic causes like translocation of chromosomes. Chromosomal translocation is rare, and associated with 2-5% of RPL. IVF allows for preimplantation genetic testing for structural rearrangements (PGT-SR) and the ability to screen embryos for abnormal chromosome number so only those with a normal set of chromosomes will be considered for transfer.  

  • IVF with preimplantation genetic testing for aneuploidy (PGT-A) may also be offered to patients with RPL given the most common cause of loss is abnormal genetics in the embryo. Some retrospective studies have shown improved live birth rates for patients with RPL using PGT-A, but there are no randomized controlled trial showing a benefit.  

  • Otherwise, the management of RPL is patient specific and focuses on trying to identify a cause of RPL specific to that patient that can be treated prior to trying to conceive again.

Last Reviewed: September 21, 2023