By Dr Geoff Reid, Endometriosis Australia's Clinical Advisory Committee
Endometriosis is estimated to affect over 500,000 women in Australia. This is probably an underestimate since approximately 40% of women with infertility will be found to have endometriosis if they proceed to a surgical procedure such as a laparoscopy (1).
Symptomatic endometriosis has a significant impact on quality of life (2). It also causes a substantial burden to the economy, estimated to be $7.7 billion dollars every year in Australia. One third of this cost is due to medical care and two thirds is due to lost productivity since women cannot continue in their usual activates of daily living. It is estimated that a woman with symptomatic endometriosis loses 10.4 hours every week in lost productivity. This puts endometriosis on a similar level with diabetes in terms of the impact that it has on women’s health.
Symptomatic endometriosis may present with period pain, pain between periods that may be cyclic or have no particular pattern, pain during or after sex, pain immediately before or during bowel movements or variations of these symptoms. Worsening of these symptoms with the onset of the period is a very common feature of endometriosis.
For many women, there is still a significant delay in diagnosis. In many countries, this remains around eight years. For women who have persistent pain that is not responsive to simple medical treatments, consideration of endometriosis should be made and appropriate referral and management undertaken (3).
In this blog I will focus on the impact of endometriosis and fertility.
What investigations should a GP perform when a woman presents with symptoms suggestive of endometriosis and infertility?
The most valuable investigation is a high quality specialised gynaecological ultrasound. Specialised ultrasound services have become increasingly reliable at diagnosing deeply invasive endometriosis (DIE), especially disease involving the bowel. They also provide information about whether organs appear to be affected by adhesions and most importantly, will diagnose ovarian endometriosis with great accuracy. They will also report an antral follicle count (this is the number of eggs starting to develop in any one cycle), which is one measure of ovarian reserve (how many eggs remain in the ovary). Many ultrasounds from ultrasound services that are not specialised ultrasound services for women may miss these important findings (4).
Another investigation is a blood test called an Anti-Müllerian Hormone (AMH) that is currently considered to be the best measure of ovarian reserve. It is important to understand that this blood does not provide information about natural fertility and it is important to discuss the results of this test with a specialist.
Other blood tests such as the CA-125 test may also be helpful, since in the absence of any disease on the ovary in a specialized ultrasound scan, an elevated CA-125 is highly suggestive of endometriosis outside of the ovary.
Other blood tests that may be performed in for fertility include a day 1-3 oestrogen and follicle stimulating hormone (FSH) test. For the FSH to be meaningful, the E2 should be less than 200 and an FSH less than 12 is desirable.
It is important to note that none of these measures of ovarian reserve predict spontaneous fertility, but they may influence a patient’s desire to move to assisted fertility, such as IVF.
When should a patient request referral to a specialist?
The decision to request a referral can be made on the basis of a woman’s symptoms alone, but if there are any abnormalities in the above investigations then specialist referral is recommended.
Women with asymptomatic infertility should be referred to an infertility specialist when basic investigations have been performed and a pregnancy has not occurred in a 12 month time period. This time should be reduced when the patient is over 35 years of age.
Who to refer to?
It is ideal for a woman with endometriosis to be referred to an infertility specialist who has access to both ART (Assisted Reproductive Technologies) and advanced excision (cutting out) surgery for endometriosis. Your general practitioner should be able to give you some guidance for this referral.
The decision about whether to use primary Assisted Reproductive Technologies (ART) or primary surgery can be very complex. In women who have both symptoms of pelvic pain and infertility, primary surgery offers a chance to improve quality of life, and may also improve chances of spontaneous fertility.
In asymptomatic women, a primary ART course should be considered, with advice to consider laparoscopy if they are not pregnant after two cycles.
How does endometriosis cause infertility?
The short answer is that it is unknown how endometriosis causes infertility, although the current theory is that endometriotic implants produce a range of chemicals that adversely affect the endometrium and reduces the chance of embryo implantation (sticking to the uterine lining to allow pregnancy to continue). Removal of these endometriotic implants therefore may be associated with improved embryo implantation. In addition, there may be effects on the ovary by endometriosis and this may affect the quality of the egg produced by the ovary.
What are the negative effects of surgery for endometriosis?
Surgical removal of endometriosis from the ovary may have an adverse impact on future ovarian reserve. Studies that we have undertaken shows that removal of a endometrioma from one ovary only will cause, on average, around a 50% drop in AMH levels. Removal of endometriomas from both ovaries will cause, on average, around a 70% drop (5) in this hormone level, suggesting a decrease in the total number of available eggs.
About 50 per cent of women having removal of ovarian endometriosis will become pregnant spontaneously in 12 months following their surgery (presuming they have patent Fallopian tubes and a partner with good quality sperm), even with these levels.
However if women don't become pregnant then ovarian surgery may have caused a catastrophic effect on the ovary’s ability to respond to ovarian stimulation in an ART setting.
This is a dilemma and makes decisions about primary surgery very difficult.
What can be done to protect ovarian reserve if a surgery is performed on the ovary for endometriosis?
Again, the short answer is nothing. Even in the best of hands, surgery may still result in severe compromise to ovarian reserve (6). There is the option of egg or embryo banking before surgery to try and have an ‘insurance policy’ should there be an issue with surgery, however these options are not without risk and also come at a cost.
Egg freezing for those without a partner is a realistic option, with excellent outcomes being reported around the world (7) in young women. For women who are over the age of 35, results are not as good and for women over 40, egg freezing is not likely to result in a viable pregnancy. Embryo freezing has been an established technology for a long time and has much better outcomes since it is further down the pathway of reproduction, but does require either a current partner of sperm donor, so is not always suitable for women who do not have a current partner.
Should you have ovarian endometriosis, then consultation with a specialist who has both expertise in endometriosis and access to ART is the best option and a full discussion of the options available to you given your specific circumstances is most appropriate. There are only a limited number of treatments available, so how you proceed will depend on your specific set of circumstances.
What can General Practitioners do for patients?
Take women with gynaecological symptoms seriously, and they will respect your care.
Ask patients about fertility worries as they may not volunteer their concerns.
Consider fertility preservation for patients with endometriosis.
Dr Geoffrey D Reid
High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Meuleman G, Vandenabeele B, et al. Fertil Steril. 2009 Jul; 92(1): 68-74
Integrating the concept of advances gynaecological imaging for endometriosis. Menakaya UA, Adno A, et al. Aust NZ J Obstet Gynaecol. 2015 Oct; 55: 409-412
Decrease in AMH after laparoscopic excision of endometrioma. Rodgers R AGES XXIV Annual Scientific Meeting Sydney, NSW Australia
Laparoscopic stripping of endometrioma negatively affects ovarian follicular reserve even if performed by experienced surgeons. Biacchiardi CP, Plane LD, et al. Reprod Biomed Online. 2011; Dec 23(6): 740-746
Consistent and predictable delivery rates after oocyte vitrification: an observational longitudinal cohort multicenter study. Reinzi L, Cobo A, et al. Hum Reprod 2012; Jun 27(6): 1606 -1612
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