Clinical Assessment and Management of the Endometrium in Recurrent Early Pregnancy Loss

Abstract

Unexplained and recurrent loss of pregnancies is a heartbreaking and frustrating condition. The routine diagnostic workup for pregnancy loss includes hormonal evaluation, screening for genetic or chromosomal defects, immunologic and thrombophilic testing, and evaluation of congenital or acquired Müllerian defects. In cases of idiopathic pregnancy loss, defects in endometrial receptivity are increasingly being investigated. The role of the endometrium in pregnancy loss has historical roots but remains controversial. Exciting new directions based on microRNAs, proteomics, and epigenetics promises to keep this area of investigation both interesting and complex. With each new diagnostic and therapeutic biomarker identified comes a greater potential for diagnosis and treatment of women. The clinical assessment of the endometrium remains an important part of the investigation of couples with unexplained pregnancy loss.

Recurrent Spontaneous Miscarriage Is Still a Challenging Diagnostic and Therapeutic Quagmire

“…The incidence of RSM in women of reproductive age seeking pregnancies is reported to be 1-2% [1,2,3,6,13,14]. RSM, which is distressing to the affected families [13] and the couple seeking parenthood, has been a formidable challenge for the treating physician [15]; it has also been regarded as a heartbreaking and frustrating condition [16]. Patients presenting with RSM have experienced psychological trauma as they face the uncertainty of the outcome of the next pregnancy, and a variety of psychological and psychiatric disorders including anxiety, depression, posttraumatic stress disorders, and obsessive-compulsive disorders develop in these patients after RSM [17].…”

Developmental exposure of fetal ovaries and fetal germ cells to endometriosis in an endometriosis model causes differential gene expression in the preimplantation embryos of the first-generation and second-generation embryos

“…Consistent with these observations, Endo rats ovulate fewer oocytes, develop fewer zygotes and at gestational day 15 have fewer viable fetuses and more pregnancy loss than Sham rats (26). In addition, Vernon MW and Wilson EA (25), the individuals who developed this endometriosis model, reported that the induction of endometriosis significantly reduced the number of pups at term by 48%.…”

“…These events included cytoplasmic fragmentation, darkened cytoplasm and arrest before syngamy, reduced embryo cell numbers (7, 11, 12). Increased frequency of embryo arrest (7, 13), decreased implantation rates (7, 11, 14, 15) and early pregnancy loss (8, 16, 17, 18, 19, 20) are also present in women with endometriosis. Yet others have not found such anomalies (21, 22, 23, 24) and this topic remains controversial.…”

“…To define which anomalies actually lead to infertility and to assess multigenerational mechanisms underlying subfertility in endometriosis which are not accessible in women, we use an established endometriosis model in the rat (Endo) compared to controls (Shams) (25). We previously reported that ovaries of Endo rats have fewer antral follicles and corpora lutea and more luteinized unruptured follicles than Sham rats (26).…”

Proteomic analysis of the sheep caruncular and intercaruncular endometrium reveals changes in functional proteins crucial for the establishment of pregnancy

“…In humans and farm animals, early pregnancy loss occurs most frequently during the peri-implantation period mainly due to uterine dysfunction and/or abnormal conceptus (embryo and extraembryonic membranes) development (Tuckerman et al 2004, Dixon et al 2007, Patel & Lessey 2011, Koot et al 2012. The incidence of early pregnancy loss in humans is estimated to be 30% prior to conceptus implantation and 30% before 6 weeks of pregnancy (Teklenburg et al 2010).…”