Dr. Christina Williams, MD FRCS (C ) (biography, no disclosures)
Clinical Associate Professor Department of Obstetrics and Gynaecology, University of British Columbia
BC Women’s Center for Pelvic Pain and Endometriosis
What I did before
In my early days as a reproductive physician, I made the diagnosis of “unexplained infertility” when ovulatory, male or tubal factors were absent. I advised the “keep trying” policy as pregnancy rates of 50% were expected in the second year of infertility (1).
I recommended a laparoscopy to diagnose and treat endometriosis as 39% of the “unexplained infertility” population have endometriosis, more when moderate or severe dysmenorrhea is present (2). After surgery, the “keep trying” policy prevailed as 1/3 of the women were expected to have an ongoing pregnancy within 9 months (3). I also recommended removal of endometriomas to improve chances of pregnancy.
IVF was always considered the “last resort”, usually recommended after failed clomiphene or gonadotropin Intrauterine Insemination (IUI) cycles.
What changed my practice?
1. Robust data on probability of pregnancy after surgical treatment of endometriosis for infertility
In 2010 the Endometriosis Fertility Index (EFI) was published (4). It combined the woman’s age, infertility duration, previous conceptions, amount of disease and status of the tubes and ovaries to give a score that predicted natural or IUI pregnancy rates (PR) at 1-2 years after endometriosis surgery for infertility.
I saw that for best prognosis couples (< 35, <3 years of infertility, normal tubes and ovaries) the PR was 58% at 12 months. If the woman> 35, PRs dropped to 38% and 10% with tubo-ovarian disease.
Diagnostic laparoscopy and cautery/excision of endometriosis is covered by MSP and is widely available through most gynaecologist in the province. Patients requiring specialized reconstructive surgery for advanced endometriosis or tubal disease would likely benefit from being referred to a gynaecologist with particular expertise in this area.
In 2013 the EFI was validated internationally by three independent international studies. When IVF outcomes were included, of 132 patients treated surgically, 67 pregnancies occurred in the following 4 years, 16 spontaneous or with IUI and 51 in IVF (5).
2. Better understanding of the concept of Ovarian Reserve
Egg supply and the length of the reproductive window can be assessed by Antimullerian Hormone (AMH) levels in blood. AMH is available through the LifeLabs in BC for a cost of approximately 75$. Levels are reported by the Lab in pMol/liter with an age related range and a prediction of how many eggs would be obtained in IVF. Previously they were reported as ng/ml (conversion 1ng/ml is 7.14 pmol/l).
AMH reflects the number of available follicles and declines as women age. Age is predictive of the “quality” of the egg (ability to produce a chromosomally normal and energy sufficient egg that will develop into a successful embryo). AMH predicts the “quantity” of eggs, meaning the amount of eggs to be expected in IVF and the length of the reproductive window, more in the line of “how much time do I have”?
Levels below 7pmol/l predict poor response in IVF (low number of eggs) and are usually seen in women around 40. Levels between 8-12 pmol/l are considered low-normal and 12-30 pmol/l are considered favourable. Levels over 30 pmol/l are seen in patients with PCOS.
Low AMH levels are not correlated with the chance of natural pregnancy. A 32 y/o with an AMH of 6 will most likely have slightly earlier menopause and produce fewer eggs in IVF, but the chances of spontaneous pregnancy are the same as another 32 y/o.
In ovarian endometriosis many publications confirmed that ovarian reserve declines after surgery to remove the cysts (6), even when best surgical technique is applied.
|Interpretation AMH levels||AMH in pmol/l|
|High (often PCOS)||Over 30|
3. Changes in IVF procedures and success rates
Recent advances in the IVF laboratory have improved the success and the safety of IVF treatment for both the women and their babies.
Vitrification (rapid freezing) (7) provides equal success with frozen embryos, significantly reducing multiple pregnancy by Sequential Single Embryo Transfer (eSET).
Comprehensive chromosomal screening (CCS) for aneuploidy is available. A recent randomized trial of single euploid eSET versus 2 untested embryos provided equal pregnancy rates (69%) with a dramatic drop in twins from 47% to 1.6% with a major reduction in low birth weight and neonatal ICU days in eSET (8).
IVF is available in BC through 5 private fertility clnics within 2-3 months from referral. There are 4 clinics in the lower mainland and 1 on the island. Kelowna offers a fertility clinic that provides satellite monitoring for IVF. A fresh cycle costs an average of 10-12,000$ including medication. A frozen embryo transfer cycle costs about 1,500$.
4. Advances in Egg Freezing
In 2014 the Canadian Fertility and Andrology Society endorsed egg freezing by vitrification. It is the chosen method of donor egg cycles worldwide (9) and widely available in Canada. Cost of egg freezing is about 7-8,000$ with ongoing storage fees.
I have learned many cases of infertility can be treated successfully, providing there is a good supply of healthy eggs. When ovarian reserve is low, natural pregnancy or egg donation are the only avenues open. The “keep trying” policy runs the risk of “running out of choices” as ovarian reserve and quality keeps dropping as time goes by.
What I do now
- I take into account historical factors (age, duration of infertility and previous conception) and assess ovarian reserve in all my infertile patients.
- I advise infertile couples to consider IVF first if the women are older (>35), have reduced ovarian reserve, long duration of infertility (more than 2 years) or have endometriomas. If IVF is not possible due to personal or financial reasons, I perform laparoscopic removal of the disease, providing the Fallopian tubes are patent. I also offer surgery to patients who have failed IVF and wish to try the natural option.
- I advise laparoscopy as first line treatment to younger couples with good ovarian reserve who wish to get pregnant naturally or need treatment for pelvic pain. I tell them IVF would most likely provide the shortest time to pregnancy. If IVF is not in their plans due to cost or personal preference for at least a year, surgery is a good option.
- For women with endometriomas not ready to consider pregnancy soon, I discuss egg freezing. I advise them that their reproductive window might be shortened and surgery might make it worse, especially if the cysts are bilateral or recurrent.
- Collins JA, Burrows EA, Willan AR. The prognosis for live birth among untreated infertile couples. Fertil Steril 1995;64:22–8. (Request with CPSBC or view UBC)
- Whitehill K, Yong PJ, Williams C. Clinical predictors of endometriosis in the infertility population: is there a better way to determine who needs a laparoscopy? J Obstet Gynaecol Can 2012 Jun;34(6):552-7. (Request with CPSBC or view UBC)
- Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis.N Engl J Med. 1997 Jul 24;337(4):217-22. (View)
- Adamson GD, Pasta DJ. Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril. 2010 Oct;94(5):1609-15. (View with CPSBC or UBC)
- Yacoub A, Ferdinus C, Mourtialon P, et al. Is Endometriosis Fertility Index a good tool to predict pregnancy in patients with surgical documented endometriosis followed by ART Management? World Congress Endo- metriosis, Montpelier, France. Clinical Free Oral Communication S#10-4. 7 September 2011.
- Flyckt R, Soto E, Falcone T. Endometriomas and Assisted Reproductive Technology. Semin Reprod Med 2013; 31(02): 164-172. (Request with CPSBC or view UBC)
- Devine K, Connell MT, Richter KS, Ramirez CI, Levens ED, DeCherney AH, Stillman RJ, Widra EA. Single vitrified blastocyst transfer maximizes liveborn children per embryo while minimizing preterm birth. Fertil Steril. 2015 Jun;103(6):1454-1460 (View with CPSBC or UBC)
- Forman EJ, Hong KH, Franasiak JM, Scott RT Jr. Obstetrical and neonatal outcomes from the BEST Trial: single embryo transfer with aneuploidy screening improves outcomes after in vitro fertilization without compromising delivery rates. Am J Obstet Gynecol. 2014 Feb;210(2):157. (View with CPSBC or UBC)
- Kalugina AS, Gabaraeva VV, Shlykova SA, Tatishcheva YA, Bystrova Comparative efficiency study of fresh and vitrified oocytes in egg donation programs for different controlled ovarian stimulation protocols. Gynecol Endocrinol. 2014 Oct;30 Suppl 1:35-8. (Request with CPSBC or view UBC)