Investigation and Management of Recurrent Pregnancy Loss: A Comprehensive Review of Guidelines
Authors: Giouleka Sonia , Tsakiridis Ioannis , Arsenaki Elisavet , Kalogiannidis Ioannis , Mamopoulos Apostolos , Papanikolaou Evangelos , Athanasiadis Apostolos , Dagklis Themistoklis 
Published: May 2023

ABSTRACT

Importance
Recurrent pregnancy loss (RPL) is one of the most frustrating clinical entities in reproductive medicine requiring not only diagnostic investigation and therapeutic intervention, but also evaluation of the risk for recurrence.

Objective
The aim of this study was to review and compare the most recently published major guidelines on investigation and management of RPL.

Evidence Acquisition
A descriptive review of guidelines from the Royal College of Obstetricians and Gynaecologists, the European Society of Human Reproduction and Embryology, the American Society for Reproductive Medicine, the French College of Gynecologists and Obstetricians, and the German, Austrian, and Swiss Society of Gynecology and Obstetrics on RPL was carried out.

Results
There is consensus among the reviewed guidelines that the mainstays of RPL investigation are a detailed personal history and screening for antiphospholipid syndrome and anatomical abnormalities of the uterus. In contrast, inherited thrombophilias, vaginal infections, and immunological and male factors of infertility are not recommended as part of a routine RPL investigation. Several differences exist regarding the necessity of the cytogenetic analysis of the products of conception, parental peripheral blood karyotyping, ovarian reserve testing, screening for thyroid disorders, diabetes or hyperhomocysteinemia, measurement of prolactin levels, and performing endometrial biopsy. Regarding the management of RPL, low-dose aspirin plus heparin is indicated for the treatment of antiphospholipid syndrome and levothyroxine for overt hypothyroidism. Genetic counseling is required in case of abnormal parental karyotype. The Royal College of Obstetricians and Gynaecologists, the European Society of Human Reproduction and Embryology, and the French College of Gynecologists and Obstetricians guidelines provide recommendations that are similar on the management of cervical insufficiency based on the previous reproductive history. However, there is no common pathway regarding the management of subclinical hypothyroidism and the surgical repair of congenital and acquired uterine anomalies. Use of heparin for inherited thrombophilias and immunotherapy and anticoagulants for unexplained RPL are not recommended, although progesterone supplementation is suggested by the American Society for Reproductive Medicine and the German, Austrian, and Swiss Society of Gynecology and Obstetrics.

Conclusions
Recurrent pregnancy loss is a devastating condition for couples. Thus, it seems of paramount importance to develop consistent international practice protocols for cost-effective investigation and management of this early pregnancy complication, with the aim to improve live birth rates.

Target Audience
Obstetricians and gynecologists, family physicians.

Learning Objectives
After participating in this activity, the learner should be better able to define recurrent pregnancy loss; explain the investigation plan for women with recurrent pregnancy loss; and evaluate the management options and propose strategies for the prevention of pregnancy loss in future pregnancies.