Endometriosis impacts 7 million women in the U.S. — three times the population of Chicago — and 10 percent of women worldwide. Unfortunately, diagnosing endometriosis remains invasive in many practices through the use of laparoscopy. Research also shows that 30 to 50 percent of women with the condition will struggle to conceive. In other words, this should be on every reproductive endocrinologist's radar.
The question becomes: What is the relationship between endometriosis and IVF, how exactly does it cause infertility and does endometriosis affect IVF outcomes?
Impacts of Endometriosis
Even though the condition is frequently overlooked or dismissed in fertility assessments, endometriosis is a critical factor in patients' fertility. According to a committee opinion by the American Society for Reproductive Medicine (ASRM), endometriosis' potential impacts on fertility include:
- Higher amount of peritoneal fluid.
- Systemic inflammation.
- Abnormal endometrial receptivity.
- Impaired embryo implantation.
- Endocrine and ovulatory abnormalities, including luteal-phase dysfunction and unruptured follicle syndrome.
- Poor egg and embryo quality.
- Slowly developing embryos.
Surgery and the Endometriosis Fertility Index
There is no cure for endometriosis, but it can be treated. If a reproductive endocrinologist suspects endometriosis or observes an endometrioma larger than 4 centimeters, laparoscopic excision surgery should be considered. Other avenues of treatment include the newly-approved medication Orilissa, which manages endometriosis pain through a gonadotropin-releasing hormone (GnRH) antagonist. Emerging research shows that antibiotics may also be a viable treatment for endometriosis.
In the past, physicians classified endometriosis — stages I through IV — based on pelvic adhesions, lesion appearance and the location of the disease. More recently, the journal Human Reproduction confirmed the Endometriosis Fertility Index (EFI) better predicts clinical outcomes following surgery. It is also endorsed by the World Endometriosis Society and the World Endometriosis Research Foundation.
The EFI rates endometriosis based on a combination of surgical observations and patient history. During surgery, doctors evaluate the patient's fallopian tubes, fimbria and ovaries on a scale of mild, moderate, severe or nonfunctional. Then they add in historical factors, including age, years infertile and prior pregnancies. All together, an EFI score of zero represents the poorest prognosis, whereas 10 represents the best.
Women with a high EFI score (9-10) may be advised to start with timed intercourse, whereas all other women may be directed toward IVF.
Does Endometriosis Affect IVF Outcomes?
In short, yes, there is a connection between endometriosis, infertility and the timing of IVF.
If patients require laparoscopic surgery, research published in The Journal of Minimally Invasive Gynecology found that they should not begin an IVF cycle until between seven and 25 months later.
What about three to six months of a GnRH agonist, like Lupron, prior to starting an IVF cycle? Although this is a popular approach, more research is needed on how it impacts egg quality.
Reproductive endocrinologists may prime IVF patients for ovarian stimulation with progesterone-based birth control pills. However, many women with the condition experience over-suppression as a result. Instead, physicians should consider Ganirelix or Cetrotide to promote proper follicular development.
Although controversial among doctors, research published in PLOS One found that the presence of endometriomas during IVF increases the risk of a poor response to stimulation. Unfortunately, patients who previously had surgery to address endometriomas are also at risk — hence the controversy.
A study published in the Journal of Ovarian Research discovered that intracytoplasmic sperm injection (ICSI) should be recommended to endometriosis patients over conventional IVF. It is suspected that fertilization rates are improved with ICSI because of the patients' poor egg quality.
Unsurprisingly, the research published in The Journal of Minimally Invasive Gynecology reported that women with severe cases of endometriosis are less likely to become pregnant following IVF.
In 2016, according to SART data, when undergoing a fresh transfer with their own eggs, the live birth rate (LBR) for women under 35 with endometriosis was 39.1 percent. In comparison, women of all ages with endometriosis who used fresh donor eggs had a 47.6 percent LBR.
The Future: Reprogramming the Uterus
While the cause of endometriosis remains unknown, we do know that defective endometrial stromal fibroblast (EMSF) cells are involved. That got researchers from Northwestern University and Tokyo's Keio University School of Medicine thinking: Can these defective cells be reprogrammed?
They published their cell replacement therapy in Stem Cell Reports and believe that these new cells can not only replace defective ones, but can also help researchers study the progression of endometriosis.
So, does endometriosis affect IVF outcomes today? Yes — and reproductive endocrinologists should not diminish all the potential impacts of the connection between endometriosis and fertility and instead treat patients accordingly. But the future looks incredibly bright.
