Clinical data confirm that more than 50% of infertile women suffer from endometriosis, and infertility accounts for 30-40% of patients with endometriosis. Whether endometriosis causes infertility is probably one of the most controversial topics in gynecology. The controversial points mainly focus on mild to moderate endometriosis. It is generally accepted that severe lesions can cause infertility because severe lesions cause changes in the pelvic anatomy, in other words, patients with severe lesions have adhesions between the fallopian tubes and ovaries, the fallopian tubes cannot pick up eggs, and there are ectopic cysts on the ovaries, which cannot ovulate normally and affect pregnancy quite understandably.
Mild to moderate endometriosis makes it difficult to get pregnant. Such cases are clinically common, and some studies suggest that the infertility rate in patients with mild to moderate endometriosis reaches 70%. However, the mechanism of infertility in patients with mild endometriosis is not exact.
I. Does mild to moderate endometriosis cause infertility?
A cross-sectional statistical analysis including 22 studies showed that the rate of follicular maturation and ovulation, the rate of implantation of fertilized eggs in the endometrium, and the rate of pregnancy were lower in patients with endometriosis than in women without endometriosis, and that these indicators were lower in patients with severe endometriosis than in those with mild endometriosis. In addition to anatomical abnormalities of the pelvis, the quality of the woman’s eggs, the maturation of the fertilized egg, and the implantation of the fertilized egg in the endometrium are all important causes of infertility.
The diagnosis of the cause of infertility needs to be made with caution because infertile women, even if other tests are normal, such as hormone levels and semen analysis, when endometriosis lesions are found in the pelvis, it does not mean that endometriosis is the cause of infertility, and some researchers have suggested the exact opposite, that mild to moderate endometriosis is an incidental finding and has no relationship to infertility.
Despite the disagreement, most still believe that mild to moderate endometriosis causes infertility. There are three main areas of research: ovarian function, germ cell delivery, and alterations in the immune system (see Table 1, Figure 1, Figure 2).
Second, why do physicians recommend expectant treatment options for patients with endometriosis infertility?
Table 7-1 lists the possible causes of infertility due to endometriosis, but most of them are of no practical value because they can also cause infertility in women without endometriosis, e.g. ovarian follicular dysplasia and anovulation in the table are themselves the main causes of infertility and not necessarily due to endometriosis. Therefore, the chance of finding mild to moderate endometriosis during the examination of infertile women is the same as the chance of finding an endometriotic lesion during the examination of women with pelvic pain, and therefore cannot be substantiated in essence.
The results of several double-blind randomized controlled studies and placebo-controlled studies do not support that endometriosis causes infertility because treatment of endometriosis with medication or surgical removal of the condition does not increase pregnancy rates.
Therefore, to date, more gynecologists prefer to advise patients to treat expectantly, i.e., to wait until they become pregnant spontaneously, especially in patients with mild to moderate endometriosis, and to be free of contraception for at least 6 months before treating endometriosis to observe whether the patient is likely to become pregnant spontaneously.
Table 7-1 Causes of infertility due to endometriosis
Ovarian function
Failure to ovulate
Abnormal follicular development
Failure to ovulate – but this is a common cause of infertility whether or not one has endometriosis.
In some patients with endometriosis, the follicles in the ovaries do not grow at a normal rate. The exact cause is not known.
Unruptured follicular luteinization syndrome (LUFS)
In patients with unruptured follicular luteinization syndrome, the follicles develop normally but the eggs are not released properly after a peak of luteinizing hormone, usually detected during laparoscopy or ultrasonography.
Oocyte abnormalities
It was once thought that the quality of eggs was reduced in patients with endometriosis, which could explain the low success rate of assisted reproduction (IVF) in patients with endometriosis. However, current studies show that IVF success rates are not low in patients with mild to moderate endometriosis.
Sperm and egg transport
Abnormal Fallopian tube function
Some related substances, such as prostaglandins produced by endometrial tissue, can affect the motor function of the muscles and cause infertility if the delivery of eggs or fertilized eggs is impaired.
Abnormalities in the anatomy of the fallopian tubes
Pelvic inflammatory disease caused by endometriosis leads to adhesions between the fallopian tubes and the surrounding pelvic organs, changes in the normal anatomy or adhesions in the inner wall of the fallopian tubes, or fibrosis in the wall of the fallopian tubes due to inflammation, all of which can lead to obstruction of egg or fertilized egg transport.
Reduced sperm viability
The inflammatory response caused by endometriosis increases the number of macrophages in the reproductive tract, which can attack sperm cells and reduce their viability in the body.
Implantation
Endometrial insufficiency
The endometrium of patients with endometriosis often lacks the factors associated with helping the fertilized egg to implant in the endometrium during the luteal phase.
Immune factors
Increased number and activity of peritoneal fluid macrophages
Increased number and activity of multiple cytokines in the peritoneal fluid of patients with endometriosis affect sperm viability, egg maturation, sperm-egg binding, fertilized egg survival, and tubal function.
Increased endometrial cytokine activity
Several related factors, such as C3 complement, HOXA10, HOXA11, and HGF, can affect fertilized egg implantation and development.
Figure 1 Pelvic and abdominal aspects of infertility in patients with endometriosis
adhesions