Cul-de-sac fluid was first described nearly a century ago by a doctor who pronounced it ordinary and routine. While it may still be relatively common today, however, this fluid faces increasing scientific inquiry as a potential indicator of infertility.
The anterior cul-de-sac is sandwiched between the bladder and uterus. The posterior cul-de-sac, also known as the pouch of Douglas, sits between the rectum and uterus. The two pelvic cul-de-sacs are the most dependent spaces in the pelvis when a patient is either upright or supine. Any cul-de-sac fluid should be easily visible on transvaginal ultrasound, which can aid in diagnosing infertility and other gynecological conditions.
What Is Cul-de-Sac Fluid?
Peritoneal fluid in the posterior cul-de-sac ebbs and flows in a cyclical fashion. The expression of ovarian vascular endothelial growth factor during the menstrual cycle increases the volume of fluid, changing from a mean of 5 ml in the early follicular phase to a mean of 20 ml in the early and midluteal phases before subsiding again, according to Fertility and Sterility. A definitive clinical threshold for a normal amount of fluid does not exist; research published in the Archives of Perinatal Medicine suggests 1 to 3 ml, or 4 to 5 ml during ovulation.
The pouch also collects menstrual blood refluxed through the fallopian tubes, along with any hemoperitoneum from ruptured ovarian cysts. Endometriosis can also affect the volume of fluid in the pouch of Douglas; patients with mild endometriosis may have higher levels of fluid, while those with severe endometriosis may have drastically less fluid than healthy patients.
Following gonadotropin therapy in infertile patients, clinical ascites may occasionally fill the cul-de-sac as a complication of ovarian hyperstimulation syndrome (OHSS). Unlike with normal fluid, the Royal College of Obstetricians and Gynaecologists recommends removing ascitic fluid through ultrasound-guided paracentesis.
The behavior and appearance of fluid on ultrasound can help to determine its cause. Echogenic fluid in either pouch may signal a ruptured ectopic pregnancy, for example. Low-level echo hemoperitoneum may indicate that a hemorrhagic cyst has ruptured.
Despite the association with pelvic pathologies, free fluid in the cul-de-sac may aid certain reproductive processes. The fluid may act as an intermediary between the ovaries while affecting fertilization, implantation and embryo development through either direct or indirect hormonal, biochemical and cellular agents.
How Cul-de-Sac Fluid Affects Fertility
While holding small to moderate amounts of fluid in the pouch of Douglas can be normal, depending on the phase of the menstrual cycle, the compounds contained in the fluid may be cause for concern. A series of recent papers suggest that the presence of specific agents in cul-de-sac fluid may foster a microenvironment that can potentially lower fertility. A study published in Fertility and Sterility lists cul-de-sac fluid containing cytokines, macrophages and angiogenic factors may thwart fertilization, implantation and embryo development. Another Fertility and Sterility study found that these same elements in the fluid "may alter the microenvironment of implantation" and lower pregnancy rates for patients undergoing controlled ovarian hyperstimulation as part of IVF.
Even before the embryo stage, free fluid may permeate the fallopian tubes and affect sperm quality. According to one study, sperm incubated in the free fluid of patients with endometriosis suffered significantly greater DNA damage compared with sperm that swam in the fluid of women without the condition. The cul-de-sac fluid of women with endometriosis was linked to reduced sperm motility and fewer progressive motile sperm. Given these results, the researchers suggest sparing sperm the "noxious" free fluid bath by encouraging patients to achieve pregnancy through IVF. Other research has found that draining the cul-de-sac of "toxic" peritoneal fluid may increase pregnancy rates for patients undergoing IVF.
The Importance of Cul-de-Sac Fluid in an Infertility Evaluation
Advances in ultrasound technology have expanded clinicians' ability to evaluate the nature and amount of fluid in the cul-de-sac to inform diagnosis. Imaging the cul-de-sac can prove valuable in assessing pelvic symptoms, supporting a diagnosis of endometriosis or probing for causes of infertility.
The same Fertility and Sterility study from above, which discovered that the cytokines, macrophages and angiogenic factors in cul-de-sac fluid may compromise implantation, also recommends imaging the cul-de-sac as a noninvasive alternative to laparoscopy to diagnose endometriosis in infertile patients. Although laparoscopy has long been the gold standard for diagnosing endometriosis, the procedure carries surgical risks and high costs. The authors found cul-de-sac fluid in 80.5 percent of women with endometriosis, suggesting that ultrasound imaging of this fluid was positively predictive of endometriosis. The researchers advise using the combination of cul-de-sac imaging and dysmenorrhea as markers to screen infertile patients at high risk for the condition.
A separate study in Fertility and Sterility recommends performing a pelvic ultrasound around cycle days five to nine to help diagnose infertility. The researchers suggest that imaging the cul-de-sac for signs of masses, endometriosis and free fluid can help patients avoid more costly exams that carry the risks of radiation and iodinated contrast exposure.
Through new research, the field of gynecology is gaining a deeper understanding of cul-de-sac fluid's role as a potential indicator of fertility. Evaluating the cul-de-sac during routine transvaginal ultrasounds can provide valuable information, particularly for patients with pelvic symptoms or infertility.
