It is generally agreed that pelvic pain occurs premenstrually in endometriosis patients. Because of this, pain from endometriosis is thought to be due to stimulation from estrogen and progesterone during the menstrual cycle; the tissue of the implant is stimulated to grow in much the same way as is the endometrium. The implants enlarge and may undergo secretory change and bleeding; however, the fibrotic tissues surrounding the implants prevent the expansion and escape of hemorrhagic fluid that occurs in the uterus. With subsequent cycles, this process repeats itself. Pain is produced by pressure and inflammation within and around the lesion, by traction on adhesions associated with the lesions, by the number of implants and their proximity to nerves and other sensitive structures, and by the mass effect of large lesions. Although this sequence of events explains why premenstrual pelvic pain can occur in endometriosis, it is incomplete, because many patients with extensive endometriosis have no pain. It is a common observation that the occurrence and severity of pain from endometriosis bear little relationship to the amount and distribution of the disease. Severe pain in patients with endometriosis is associated with deeply infiltrating lesions, and it is thought that the degree of pain is perhaps determined by the depth of invasion.

The relationship between endometriosis and infertility has been more extensively investigated. Moderate and severe endometriosis is associated with pelvic adhesions that distort pelvic anatomy, prevent normal tubo-ovarian apposition, and encase the ovary. Implants can destroy ovarian and tubal tissue, although occlusion of uterine tubes is rare.

It is not difficult to understand how advanced disease can result in infertility, but minimal or mild endometriosis, in which pelvic anatomy is entirely normal except for a few peritoneal surface lesions, can also cause infertility. The mechanism by which this occurs is unknown. Various theories have been proposed to explain this phenomenon.

Several investigators have examined peritoneal fluid abnormalities. The peritoneal fluid is an ultrafiltrate of plasma, with less than 5 mL normally present in the pelvis. After ovulation, a transient rise to approximately 20 mL occurs. The volume of peritoneal fluid and the concentrations of various hormones and other substances in it affect the processes of ovulation, ovum pickup, tubal function, and so on. The normal role of the peritoneal fluid and its constituents in these processes, and how it is altered by endometriosis, are largely unknown. Peritoneal fluid volume has been reported to be altered in endometriosis patients, but studies have led to inconsistent results.

Similarly, reports are contradictory as to whether endometriosis patients have elevations in peritoneal fluid prostaglandins F₂ and E₂. Prostaglandins are normally secreted by the endometrium and by endometriosis lesions; an increase in peritoneal fluid prostaglandin levels could theoretically decrease fertility by altering ovulation, tubal motility, nidation, and luteal phase adequacy. The conflicting reports may result from fluctuations that normally occur across the cycle in prostanoid production, as well as variations in the lesions’ synthesis of prostaglandins; small red petechial implants have been found to secrete more prostaglandins than larger, powder burn-like ones.

Several disorders of menstrual cyclicity and ovulation have been suggested as a basis for the infertility caused by mild endometriosis. The rate of ovulation among endometriosis patients is 11-27%. Nearly half become pregnant when this problem is also treated. More subtle problems in folliculogenesis in endometriosis patients have been reported, including lower serum estradiol levels, smaller follicle size during follicular growth, and lower oocyte fertilization rates and pregnancy rates in assisted reproduction. Problems with ovum pickup by the fallopian tube and embryo implantation in the endometrium have also been suggested.

As noted previously, deficient cellular immunity to endometrium has been reported in endometriosis. This may also adversely affect normal nidation and other reproductive processes. Other studies have shown that the number or activity of peritoneal macrophages may be increased in endometriosis, possibly causing excessive prostaglandins to be released locally by the macrophages, causing sperm transport or function to be attacked by the cells, and cytokines (inflammatory mediators including interleukin-1) to be released from pelvic lymphocytes.