Thrombophilias, a cause of implantation failure and repeat miscarriages?

By (embryologist), (gynecologist) and (embryologist).
Last Update: 04/10/2023

Repeat miscarriage is defined as the loss of three consecutive pregnancies before 20 weeks, although more and more specialists choose to consider it as recurrent miscarriage after two consecutive gestational losses.

This is a complicated situation, since the cause is not always known. Almost 50% of recurrent abortions are of unknown origin. Repeated miscarriage should be treated as a complex disease in which several factors may be intervening at the same time, preventing the pregnancy from reaching full term.

More and more specialists are paying attention to blood clotting factors, as they suspect that thrombophilias may be involved in repeat miscarriage and implantation failure.

What are thrombophilias?

Thrombophilia is a pathology characterized by a fairly easy blood clotting, which leads to the rapid formation of clots. Therefore, thrombophilia is an increase in blood coagulation, leading to thrombus formation.

There are two types of thrombophilias:

represented mainly by antiphospholipid syndrome (APS).
caused by alterations at the gene level, such as a mutation in Factor II or Factor V, factors involved in the coagulation cascade.

These types of blood disorders are targeted in patients who have suffered several miscarriages and implantation failures. Several studies have concluded that there is a possible relationship between blood coagulation disorders and pregnancy complications and miscarriages. However, there are no robust conclusions in the studies, except for the antiphospholipid syndrome.

Symptoms of thrombophilia

Thrombophilia is considered the silent disease, since it rarely causes symptoms. Most patients diagnosed with thrombophilias do not develop visible discomfort.

Instead, in some cases, these patients may have leg swelling and ankle pain because a thrombus is occurring. This is usually accompanied by fever and/or heat in the area.

Tests in the diagnosis of thrombophilia

The diagnosis of thrombophilia does not consist solely of a conventional blood test, but requires specific thrombophilia tests.

These tests are expensive, but in addition to providing information on altered clotting factors, they also provide information on genes involved in the blood system and blood circulation. Some of the tests include the study of specific blood antibodies, factor V Leiden, factor VIII, factor XIII, homocysteine, genes involved in blood group type (ABO genotype) and polymorphisms in coagulation factors.

Thrombophilias and pregnancy

Throughout gestation, physiological changes occur in several coagulation factors. The main consequence of this is that there is an increased risk of thrombus.

If the patient suffers from thrombophilia, it is possible that her pregnancy may not be carried to term. Only 5% of them succeed. On the other hand, if the patient is being treated or treatment is established after the diagnosis of thrombophilia, there is an 85% chance that the pregnancy will be carried to term.

In any case, pregnancies in patients with thrombophilias are high risk. Therefore, an exhaustive monitoring of gestation is necessary.

Blood coagulation study

During pregnancy, hemostatic changes occur in women. This means that in pregnancy some blood factors are altered. For example, coagulation factors FI, FVII, FVIII, FIX and FX, protein C activity increase; while protein S concentration decreases. In addition, other chain reactions occur that eventually generate thrombin, a protein that is synthesized during coagulation.

Thrombin may act to cause gestational loss as follows:

  • Triggering an inflammatory response through the release of cytokines, also involving the immune system and causing early loss.
  • Producing small thrombi in the vessels that irrigate the placenta, causing placental insufficiency, which is related tomiscarriages from the 10th week of gestation.

However, the association between thrombotic problems and repeat miscarriages remains doubtful at present.

Preventing abortion

Women with thrombophilic disorders often have a difficult reproductive history, such as: difficulty in achieving pregnancy, repeated IVF failures, multiple biochemical pregnancies or repeated miscarriages.

In patients with thrombophilias, bringing a pregnancy to term and delivering the baby can be a challenge for specialists. It is recommended that the gynecologist works together with the hematologist to control the alterations in blood coagulation so that the baby can develop and reach the moment of delivery.

More and more studies support the use of aspirin and heparin to treat women with thrombophilias during pregnancy. If medication is applied from the time of ovarian stimulation, many benefits are observed. Despite this, the role of heparin is also questionable.

These pregnancies are usually complicated, so bleeding is more common and especially during the first trimester the specialist may advise absolute rest to avoid gestational loss.

Following the instructions of the specialists, gynecologist, obstetrician and hetamologist, as well as taking medication carefully, can make all the difference in achieving the birth.

FAQs from users

What tests are included in the repeat miscarriage study?

By Guillermo Quea Campos M.D. (gynecologist).

Normally, the study of repeated miscarriages consists of an analysis of the Antiphospholipid Syndrome, genetic testing, assessment of thrombophilias, hysteroscopy, and transvaginal ultrasound to study anatomy.
Read more

When is a thrombophilia study indicated?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

The thrombophilia study can be performed at any time, since it does not interfere during a possible pregnancy. However, in patients with repeated miscarriages and implantation failures, more and more specialists are opting for thrombophilia testing.

Are all cases of recurrent miscarriages due to coagulation problems?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

No. Repeated miscarriages can have different reasons and it is thought that one of them could be thrombophilias or blood clotting problems.

This is why many specialists recommend specific tests in case there could be a link. However, conclusions about this association are limited.

Does thrombophilia cause female infertility?

By Marta Barranquero Gómez B.Sc., M.Sc. (embryologist).

No. Women diagnosed with thrombophilia can achieve pregnancy. However, it is important to monitor the pregnancy since there is a higher risk of miscarriage than if there were no blood clotting problems.

Suggested for you

Thrombophilia may be the reason for recurrent miscarriages, but this is not always the case. If you would like to learn more about recurrent gestational loss, we recommend you visit the following article: What is recurrent miscarriage - Causes, diagnosis and treatment.

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Amy M Adelberg, Jeffrey A Kuller. Thrombophilias and recurrent miscarriage. Obstet Gynecol Surv. 2002 Oct;57(10):703-9. doi: 10.1097/00006254-200210000-00024.

Ineke Krabbendam 1, Arie Franx, Michiel L Bots, Rob Fijnheer, Hein W Bruinse. Thrombophilias and recurrent pregnancy loss: a critical appraisal of the literature. Eur J Obstet Gynecol Reprod Biol. 2005 Feb 1;118(2):143-53.

Paulien G de Jong, Stef Kaandorp, Marcello Di Nisio, Mariëtte Goddijn, Saskia Middeldorp. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev. 2014 Jul 4;2014(7):CD004734 (View)

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Xiaoling Liu, Yan Chen, Changxiang Ye, Dexiu Xing, Rong Wu, Fang Li, Lizhang Chen, Tingting Wang. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod. 2021 Apr 20;36(5):1213-1229. doi: 10.1093/humrep/deab010.

FAQs from users: 'What tests are included in the repeat miscarriage study?', 'When is a thrombophilia study indicated?', 'Are all cases of recurrent miscarriages due to coagulation problems?' and 'Does thrombophilia cause female infertility?'.

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Authors and contributors

 Cristina Mestre Ferrer
Cristina Mestre Ferrer
B.Sc., M.Sc.
Bachelor's Degree in Biological Sciences, Genetics & Human Reproduction from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Embryologist at IVI Barcelona. More information about Cristina Mestre Ferrer
 Guillermo Quea Campos
Guillermo Quea Campos
Guillermo Quea, MD has a degree in Medicine and Surgery from the University of San Martin de Porres. He also has a Master's Degree in Human Reproduction from the Universidad Rey Juan Carlos and another in Public Health and Preventive Medicine from the Universidad del País Vasco. More information about Guillermo Quea Campos
Member number: 282860962
 Marta Barranquero Gómez
Marta Barranquero Gómez
B.Sc., M.Sc.
Graduated in Biochemistry and Biomedical Sciences by the University of Valencia (UV) and specialized in Assisted Reproduction by the University of Alcalá de Henares (UAH) in collaboration with Ginefiv and in Clinical Genetics by the University of Alcalá de Henares (UAH). More information about Marta Barranquero Gómez
License: 3316-CV

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