Abstract
Uterine and tubal abnormalities alone or in combination with other factors are present in 17%–25% of all couples who seek care for infertility treatment. The prevalence is higher in older women and in those with secondary infertility. Although suspected at the history, it is usually confirmed by ultrasound/ laparoscopy and/or MRI depending on the cause. Multiple pathologies are identified under the umbrella of tubal and uterine factors, some are associated with infertility but very few are proven to be the only cause of infertility. Treatment depends on the condition. It ranges from no intervention to surgery to in vitro fertilisation (IVF). With advances in the technology of IVF, surgery is becoming a lost art, especially for tubal factors. Various surgical techniques have been suggested for uterine factors. Given most tubal and uterine factors have association rather than causation for infertility, the effect of surgery on improving fertility is debatable. We will discuss the causes of uterine and tubal factors, their implications on fertility, diagnostic modalities and treatment options with limitations of the available evidence. A good history and a high index of suspicion along with primary and secondary prevention of tubal and uterine factor infertility are important to prevent long-term implications.
4.1 Background
Tubal abnormalities alone or in combination with other factors account for 17%–25% of all couples who present with infertility. Their prevalence is higher in older women and those with secondary infertility [1].
Restriction of tubal function due to pelvic adhesions or tubal damage (in the form of occlusion or fibrosis) results in impairment of the ability of the fallopian tube to effectively transport an egg or embryo to the uterus. The amount of damage can vary greatly in extent, anatomical location and nature. Tubal disease can involve the proximal, distal or entire tube and varies in severity.
Abnormalities of uterine anatomy or function are relatively uncommon causes of infertility but should be considered through appropriate history and investigation.
4.2 Causes of Tubal Factor Infertility
There are multiple conditions associated with uterine and tubal factor infertility (Table 4.1). Pelvic inflammatory disease (PID) is the most common cause of tubal disease, representing more than 50% of cases, and may affect the fallopian tube at multiple sites. The most common infective agent involved is Chlamydia trachomatis. The risk of acquiring chlamydial infection is increased through multiple sexual partners.
| Tubal | Uterine |
|---|---|
| Pelvic inflammatory disease | Endometriosis |
| Past Chlamydia infection | Adenomyosis |
| Multiple sexual partners | Uterine septum |
| Previous pelvic surgery | Polyps |
| Previous ruptured appendix | Fibroids |
| History of inflammatory bowel disease | Intrauterine adhesions (Asherman’s syndrome) |
| Previous ectopic pregnancy | Mullerian anomalies |
Previous extensive pelvic surgery can lead to altered anatomy and the formation of tubal adhesions leading to tubal blockage. Appendicitis leading to peritonitis is a classic example where significant adhesions may form involving the fallopian tubes. Even if the adhesions formed appear to involve only one tube, it is possible that the contralateral tube although macroscopically normal may be compromised. This is similar to the situation which might arise following an ectopic pregnancy.
One of the challenges facing clinicians is the fact that following elaborate investigations (including tubal assessment), it is often difficult to provide infertile couples with an accurate prognosis. For women with infertility due to tubal disease, predicting the chance of pregnancy with or without corrective surgery often remains imprecise. There is no universally accepted classification of tubal disease severity to provide comparability of published results. It is acknowledged that the chances of conception are low in women with bilateral tubal occlusion and good in women with patent tubes with few filmy adhesions. The Hull & Rutherford classification [2] is a simple classification system that separates infertile women into three categories according to the severity of tubal damage (Table 4.2).
| Class | Name | Description |
|---|---|---|
| 1 | Minor/grade I |
|
| 2 | Intermediate or moderate/grade II |
|
| 3 | Severe/grade III |
|
Other classification systems have been designed including those from the American Fertility Society [3], Akande [4] and others. Although, such systems are descriptive of the extent of disease, there remains a lack of robust data to correlate with prognosis.
4.3 Other Pelvic Pathology
4.3.1 Fibroids
Uterine leiomyomas, commonly called fibroids, occur, to varying degree, in as many as 20% of women of reproductive age. Fibroids are benign tumours of smooth muscle growing within the uterus. Malignant transformation is very rare. Various classification systems of fibroids exist usually based on the location of the tumour within the uterus (submucosal, intramural and subserosal). Further subdivisions based on the proportion of the fibroid within the uterine muscle wall at each location are shown in Figure 4.1 and used by most societies and research trials.
Figure 4.1 Classification of fibroids.
How much impact fibroids have on fertility has been a matter of debate. It is unclear as to whether the finding of fibroids in infertile women is incidental or causative. In addition, there is controversy as to whether the association applies only to the chances of spontaneous conception or has a bearing on the outcome of fertility treatment. Some of the reasons for controversy within the literature relate to the variety of types of fibroids, inconsistency of the nomenclature used, heterogeneity in study design and a lack of appropriately powered randomised trials. Despite these concerns it is accepted that fibroids are associated with infertility. Various causes have been postulated for this (Table 4.3). It is most probably a combination of factors that contributes to any associated fertility difficulties. However, the literature is inconsistent in assessing the impact that such disturbances might have on the likelihood of achieving and maintaining pregnancy (with or without fertility treatment).
Table 4.3 Mechanisms by which fibroids may impair fertility
| Deformity of the cavity may affect implantation |
| Mechanical obstruction of the ostia of fallopian tubes |
| Chronic inflammatory response within the endometrium |
| Disordered uterine contractility associated with intramural fibroids |
| Endometrial atrophy due to pressure from a fibroid mass |
4.3.2 Endometriosis
Endometriosis encompasses a spectrum of disease ranging from minimal to severe. Many women with minimal and mild endometriosis experience no difficulty in conceiving. It is not unusual for parous women undergoing sterilisation to be noted to have endometriosis. However, it appears that the prevalence of endometriosis is higher in women attending fertility clinics compared to that in the general population, with some studies quoting up to 50%.
There is dispute over whether minimal/mild endometriosis is a causal finding in couples with infertility and whether or not treatment of this degree of endometriosis is of benefit. Moderate or severe endometriosis involving adhesions or ovarian cysts may impair fertility by inhibiting ovulation and/or ovum ‘pick-up’ by the Fallopian tubes. However, in studies involving infertile couples, the finding of minimal and mild endometriosis seems to be an added negative fertility factor. The exact mechanism of this negative fertility factor is unclear but various possible mechanisms have been postulated. Endometriosis as an issue in infertility is explored in more detail in Chapter 3.
4.3.3 Adenomyosis
Although often discovered in parous women, adenomyosis has been found to be associated with infertility. This is mainly due to effects on implantation. It is estimated that one third of all cases of endometriosis are associated with adenomyosis. However, studies on adenomyosis are limited in infertility populations and are frequently confounded by the presence of other factors. In the absence of agreed diagnostic criteria and the failure of national registries to consistently include the diagnosis, the exact prevalence and strength of the association of adenomyosis with infertility are not known.
4.3.4 Endometrial Polyps
It is estimated that uterine polyps are found in 10% of the general female population. Endometrial polyps are frequently seen in subfertile women, and there is some evidence suggesting a detrimental effect on fertility. How polyps contribute to subfertility and pregnancy loss is uncertain and possible mechanisms are poorly understood. It may be related to mechanical interference with sperm transport, embryo implantation or through intrauterine inflammation or altered production of endometrial receptivity factors.
4.3.5 Structural Uterine Abnormalities
Structural uterine anomalies are usually derived from deviation in development of mullerian or paramesonephric ducts. Abnormalities of uterine anatomy are relatively uncommon causes of infertility in women. Their effect on reproduction depend on type and degree. An internationally accepted classification has been produced by joint consensus between the European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Gynaecological Endoscopy (ESGE) [6]. Anomalies are classified into main classes (Figure 4.2) expressing uterine anatomical deviations deriving from the same embryological origin. These are subdivided into subclasses expressing anatomical varieties with clinical significance. Cervical and vaginal anomalies are classified independently into subclasses having clinical significance.
It is difficult to ascertain whether such anomalies cause, or are just associated, with infertility given that there are often other factors associated with the infertility along with these findings. The location and degree of abnormality are also variable. Irrespective of this uncertainty, it is important to identify if these abnormalities are present, as they have implications for obstetric care as well as some aspects of fertility treatments. Mullerian anomalies are associated in a third of cases with renal and spinal cord abnormalities, the absence of one kidney being the most common abnormality.
4.3.6 Intrauterine Adhesions
The presence of adhesions within the uterine cavity may have profound effects on reproductive potential. The term Asherman’s syndrome (AS) describes the clinical situation of absent or light periods, sometimes associated with pain and an inability to conceive consequent on damage to the endometrial cavity usually following curettage. AS causes infertility by reducing implantation potential.
While the degree of severity of intrauterine adhesions may be assessed by hysterosalpingography, in more recent years classifications systems have been developed based on hysteroscopy, now the gold standard to diagnose AS. The widely used AFS system includes an assessment of the extent of the disease, menstrual pattern and the density of the adhesions. Both hysteroscopy and hysterosalpingography could be used for this kind of scoring system (Figure 4.3).
4.4 Diagnosis
4.4.1 History Taking
A good structured history from the female partner is essential in evaluating the risk of uterine and tubal factors. A history of ectopic pregnancy, pelvic inflammatory disease (PID), endometriosis or prior pelvic surgery raises the index of suspicion for tubal factor infertility.
All patients in the fertility clinic should be asked these specific questions (Table 4.4). If endometriosis is suspected, it is essential to explore a history of dyspareunia, pain or difficulty at defaecation (dyschezia), or bleeding per rectum. These symptoms will assist in determining the potential extent of pathology as well as direct appropriate investigations. The impact symptoms have on quality of life should be evaluated at the initial consultation as that will influence decision making as to whether to treat pathology or proceed with fertility treatment.
