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Structural uterine anomalies in recurrent pregnancy loss

Pregnancy loss, especially when recurrent is an emotionally traumatic experience. Recurrent pregnancy loss (RPL), habitual abortion or recurrent miscarriage is defined as the occurrence of three or more consecutive pregnancies that end in miscarriage of the fetus before the age of viability i.e. 20 weeks. About 15% of couples lose one recognized pregnancy and 2% of couples lose two. Studies suggest that the risk of miscarriage in subsequent pregnancies is 30% after two losses compared with 33% after three losses among patients without a history of live birth. It has been reported that 1-3% of women experience recurrent loss of pregnancy and the cause is not identified in approximately 50% of cases. Of the identifiable causes, chromosomal disorders like translocation and aneuploidy are responsible for 2-5% cases while as anatomic factors account for 10-15% of cases.


INTRODUCTION
Pregnancy loss, especially when recurrent is an emotionally traumatic experience. Recurrent pregnancy loss (RPL), habitual abortion or recurrent miscarriage is defined as the occurrence of three or more consecutive pregnancies that end in miscarriage of the fetus before the age of viability i.e. 20 weeks. 1 About 15% of couples lose one recognized pregnancy and 2% of couples lose two. 2 Studies suggest that the risk of miscarriage in subsequent pregnancies is 30% after two losses compared with 33% after three losses among patients without a history of live birth. 3 It has been reported that 1-3% of women experience recurrent loss of pregnancy and the cause is not identified in approximately 50% of cases. 4 Of the identifiable causes, chromosomal disorders like translocation and aneuploidy are responsible for 2-5% cases while as anatomic factors account for 10-15% of cases.
Uterine anomalies are directly associated with recurrent pregnancy loss and can be divided into congenital and acquired forms. Congenital anomalies include fusion abnormalities or partial agenesis of developing uterus such as septate, bicornuate, didelphis or unicornuate uterus. 5 Furthermore, a number of acquired uterine anomalies such as fibroids, intrauterine adhesions, Asherman syndrome, endometrial polyps, adenomyosis, endometriosis and cervical incompetence have been associated with recurrent pregnancy loss. 6 During development, the uterus forms via the apposition of a portion of bilateral hollow tubes called mullerian ducts. The dissolution of the walls of these ducts along their sites of apposition allows formation of intrauterine cavity, the intracervical canal and the upper vagina. Congenital uterine anomalies may therefore include incomplete mullerian duct fusion, incomplete septum and uterine cervical anomalies. Congenital uterine anomalies may arise from malformations at any step of the mullerian developmental process. 7 Buttram and Gibbons first proposed a classification of the congenital uterine anomalies based on the degree of failure of the mullerian ducts to develop normally, and divided them into groups with similar clinical manifestations, treatment and prognosis. This was revised and modified first in 1983 and then in 1988 by the American society of reproductive medicine to provide a classification which is now the most widely accepted and used worldwide. This consists of seven groups, some with further subdivisions: Diethylstilbestrol (DES) exposed uterus (t-shaped uterus resulting from DES exposure of the patient in utero) Women with an intrauterine septum may have as high as 60% risk of spontaneous abortion. Uterine septum related losses most frequently occur during the second trimester, however, if an embryo implants into the poorly developed endometrium overlying the uterine septum, abnormal placentation and resultant first trimester losses may occur.
The prevalence of arcuate uterus in women with recurrent pregnancy loss is 12.2%, such high prevalence suggests causal relation between arcuate uterus and recurrent pregnancy loss. 8 Cervical incompetence classically causes losses in the second trimester (gestational weeks 12 to 28). It is associated with painless cervical dilatation and expulsion of the fetus. The diagnosis requires two consecutive losses. Cervical incompetence can be caused by congenital factors (e.g., DES exposure), trauma (including forceps delivery, especially if performed before full dilatation is complete), and surgical procedures (e.g., cervical cone biopsies, laser procedures, and loop electrocautery excision procedures). The chance of carrying the baby to term can be improved by placing a cervical cerclage at 10 to 14 weeks, after fetal viability has been confirmed. 2 Asherman syndrome is also associated with recurrent miscarriage. 9 The presence of intrauterine adhesions may significantly impact placentation and result in early pregnancy loss.
Fibroids distort the endometrial cavity and impede the implantation. Intramural fibroids larger than 5 cm in size as well as submucosal fibroids of any size can cause recurrent pregnancy loss.
The septate uterus is most commonly associated with reproductive failure. 10 Hysterosalpingography (HSG) may reveal two hemi cavities, without visualization of uterine fundus and may be indistinguishable from a bicornuate uterus. Although HSG remains a useful tool for diagnosis of a normal or abnormal uterine cavity, it cannot reliably differentiate between different types of structural uterine anomalies and allow appropriate classification. 11,12 Although 3D ultrasound has been used in diagnosis of septate uterus only a few studies are available with no definite conclusion and its role in identification of uterine septum. 13 Combining diagnostic modalities can improve diagnostic accuracy but concurrent hysteroscopy and laparoscopy remains the gold standard for diagnosis of septate uterus. 3

METHODS
This prospective observational study was conducted in a tertiary care hospital over a period of one and half year.

Inclusion criteria
• Women with three or more consecutive spontaneous pregnancy losses were included in this study

Exclusion criteria
• Patients with established diagnosis of recurrent pregnancy loss due to endocrine, autoimmune or genetic causes and patients with major medical illness (liver disease, diabetes) coagulation disorders or on oral anti-coagulant therapy were excluded.
Women included were counseled and informed about the method of this study. They were subjected to detailed medical, surgical, family, obstetric and gynecological histories.
A detailed physical examination was carried out. All prior pregnancies were assessed with attention to gestational age at time of loss, complications and pathology reports, if any pelvic ultrasonography and hysterosalpingograms were accessed and evaluated.
All base line and specific investigations to rule out autoimmune, endocrine and genetic causes of recurrent pregnancy loss were done. Serum progesterone (mid luteal progesterone on day 21 of 28-day cycle) was done to rule out luteal phase defect as a cause of recurrent pregnancy loss. Serum prolactin and thyroid function tests were carried out to exclude hyperprolactinemia and thyroid function abnormalities. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 was also done. Transvaginal and transabdominal sonography was carried out before the procedure. All patients recruited for the study were admitted 2 days prior to the procedure, in post menstrual period as during early proliferative phase uterine cavity is easily evaluated. Preanaesthetic evaluation was carried out. Combined hysteroscopy and laparoscopy were carried out after written informed consent from the patient.
There were no intraoperative or postoperative complications noted in this study.  14,16 In the hysteroscopic findings in present study septum was found in 10 patients (25%), which was the most common finding, submucous myoma was present in 8 patients (20%),polyp was found in 5 patients accounting for 12.5% of the patients, whereas 3 patients (

CONCLUSION
In present study hysteroscopy was abnormal in 67.5% patients with most common finding being uterine septum followed by submucous fibroid and polyp. Intra uterine adhesions and cervical incompetence were the less common findings on hysteroscopy. Laparoscopy was normal in 65% of patients whereas only 35% of patients had abnormal laparoscopic findings. Endometriosis was the most common abnormal finding on laparoscopy followed by intrapelvic adhesions and bicornuate uterus.5% of patients had abnormal findings both on hysteroscopy and laparoscopy.Thus, concluding that women with recurrent pregnancy loss have increased association with structural uterine anomalies than general population. Both congenital and acquired uterine anomalies are associated with recurrent abortions.