What is Endometriosis?

Endometriosis is a benign and oestrogen-dependent gynaecological disorder with tissues (glandular and stromal) that normally line the cavity of the uterus growing in ectopic sites (predominantly in the pelvic cavity, ovarian surface and the rectovaginal septum). These “displaced” endometrial tissues follow the menstrual cycle and proliferate, break down and bleed, causing painful periods, pain with sexual intercourse, defecation and micturition as well as scarring and adhesions to nearby organs. Endometriosis affecting the ovaries – often known as endometriomas or chocolate cysts – has a high relapse rate and the condition usually resolves with onset of the menopause. Infertility is a major complication. Although the exact cause of endometriosis is uncertain, retrograde menstruation via the fallopian tubes into the pelvic cavity may be one of the explanation³.

Conventional Treatment

Treatment for endometriosis includes analgesic, hormones to slow endometrial tissue growth, such as oestrogen and progestin, progestin alone and gonadotropin-releasing hormone agonist (GnRH agonist), surgery to remove ovarian endometriomas and to restore normal pelvic anatomical relationship, and definitive surgery (pelvic clearance – complete excision of reproductive organs) to induce a surgical menopause³. Studies have shown that 20.5% to 43.5% of endometriosis patients recurred within five years after conservative surgery and the recurrence rate increased persistently over time after the first surgery unless definitive surgery has been performed^3-5. “There was a time when repeated and eventually definitive surgery were performed in an attempt to “eradicate” endometriosis. By such, patients’ prognosis, quality of life and family planning could hardly be well served,” said Dr. So.

Limitations of Conservative Surgery

In recent years, the media have empowered patients to be more knowledgeable and mindful of treatment outcome and prognosis. With the widespread availability of pelvic ultrasound and minimal-access surgery, diagnosis and removal of endometriotic cysts, irrespective of size, has become more prevalent⁶. “Treatment option for pelvic endometriosis depends on whether it is symptomatic, patient’s age, the site and severity of endometriosis, previous operative history, medical risks with surgery and patient’s desire to preserve childbearing ability. Often patients are unaware of the detrimental effects of surgery on ovarian reserve and future fertility,” Dr. So explained. “Surgical excision of ovarian endometrioma by any technique invariably affects ovarian reserve with a decrease in serum AMH levels, reduced frequency of spontaneous ovulation and higher doses of gonadotrophins for controlled ovarian stimulation with less oocytes retrieved and nearly thrice the cycle cancellation rate because of poor ovarian response. These effects are more pronounced in cases of bilateral and recurrent endometriomas,” he added. The American Society of Clinical Oncology (ASCO) guidelines have recommended oncologists to inform cancer patients about potential treatment-related threat to ovarian reserve and infertility before treatment⁷. By the same token, considering that fertility declines over time because endometriomas negatively impacts ovarian reserve regardless of surgical intervention, fertility preservation should be on the main agenda in endometriosis management^1,8.

Fertility Preservation Fosters Family Planning

Since the birth of the world’s first in-vitro fertilisation (IVF) baby in England in 1978 and Hong Kong’s first in 1987, research and development in assisted reproduction has flourished^9,10. Fast forward to the present, cryopreservation of embryos and gametes has become standard practice and has led to an increased awareness of fertility preservation for medical conditions that might threaten ovarian reserve. Young cancer patients undergoing chemotherapy or radiotherapy that might be gonadotoxic are prime examples. These patients can now freeze their eggs or sperms prior to cancer treatment in order to preserve their future fertility potential. Some reproductive medicine specialists also believe the same for women with endometriomas prior to surgery. Moreover, there is a paradigm shift towards a more conservative approach in the management of ovarian endometriomas.

Cryopreservation in Hong Kong

Fertility preservation involves the freezing of gametes (sperms or oocytes) or embryos, and in some situations, gonadal tissue to preserve a person’s future fertility¹¹. Studies reveal that ovarian tissue cryopreservation (OTC) enables children or young patients to store a larger number of primordial follicles, which can restore ovarian endocrine function and possibly lead to a higher fertility success rate in the future¹². According to Jadoul et al (2017), more than 86 live births by OTC have been reported globally as of 2017¹³. Yet, as the number of healthy and quality oocyte is pivotal, OTC is less effective in restoring fertility for patients in the older age group because their follicle density is relatively low when tissue is preserved¹². Furthermore, OTC is still considered experimental in many countries including Hong Kong.

While OTC remains experimental, oocyte and embryo cryopreservation are the customary options that can yield a successful pregnancy¹¹. Studies reported survival rates of 80% to 90% and 90% for oocytes and embryos after freezing and thawing respectively. Besides, oocyte vitrification is now considered a standard procedure in many IVF laboratories worldwide^14-16.

Doctor-Patient Dialogue

Recently, a questionnaire survey was conducted on the awareness of and barriers to fertility preservation among clinicians in the departments of Clinical Oncology, Obstetrics and Gynaecology, Haematology, Paediatrics and Surgery in various public hospitals in Hong Kong. Almost all clinicians agreed to setting up a dedicated fertility preservation centre and 76.5% agreed that fertility preservation should be provided as a public service¹⁷. Nonetheless, only 31.7% of clinicians had ever referred a patient for fertility preservation¹⁷. The reasons for low referral include poor prognosis, lack of available time prior to treatment, considerable risk of recurrence, need for treatment as first priority and financial constraints¹⁷.

To fully utilise fertility preservation as a resource to optimise endometriosis management, in-depth, unbiased and up-to-date counselling is of paramount importance. “Nowadays, doctors are more forthcoming in discussing treatment options with patients. Patients with endometriosis, because of the chronic and recurrent nature of the disease and its long-term impact on fertility, should consider more comprehensive and long-term management options that can maximise their fertility potential before simply deciding on surgery. This is particularly important to asymptomatic, young women with incidental finding of ovarian endometriomas less than 4 cm in diameter,” Dr. So commented.

Individualized Management Yields Better Outcome

Technological advancement and improved public health education have enabled early screening and diagnosis of diseases. A study from Finland demonstrates decreased median age of patients with endometriosis; this finding echoes that observed in Hong Kong⁶. While fertility preservation may be one option, there are still many unanswered questions regarding its timing; the pros and cons of oocyte vitrification, embryo or ovarian tissue cryopreservation as opposed to prompt fertility assistance such as IVF. “Informed choices on family planning such as attempting pregnancy at an earlier age before diminished ovarian reserve sets in, medical therapy and fertility sparing surgery in skilled hands may all be alternatives in the holistic management of endometriosis depending on the age of the patient, whether she has a partner, whether she is symptomatic, her life goals and financial situation,” said Dr. So.

References

1. Barnett R, et al. Clin Obstet Gynecol. 2017; 60(3): 517-523. 2. Hospital Authority. Hospital Authority Statistic Report 2016-2017. 3. Donnez J, et al. Minerva Ginecol. 2018; 70(4): 408-414. 4. Obstetrical and Gynaecological Society of Malaysia. Clinical Guidelines for the Management of Endometriosis. 2016. 5. Selçuk I, et al. J Turk Ger Gynecol Assoc. 2013; 14(2): 98-103. 6. Tandoi I, et al. J Pediatr Adolesc Gynecol. 2011; 24(6): 376-379. 7. Saavalainen L, et al. Acta Obstet Gynecol Scand. 2018; 97(1): 59-67. 8. Lee SJ, et al. J Clin Oncol. 2006; 24(18): 2917-2931. 9. Steptoe PC, et al. Lancet. 1978; 2:366. 10. IVFHK. Available at: https://www.ivfhk.com/about-us-3/milestones/ (Accessed on 11 Oct 2019). 11. Kato A. Reprod Med Biol. 2016; 15(4): 227-233. 12. Donfack NJ, et al. Zygote. 2017; 25(4): 391-403. 13. Jadoul P, et al. Hum Reprod. 2017; 32: 1046-1054. 14. Saumet J, et al. JOGC. 2018; 40(3): 356-368. 15. Mayo Clinic. Available at: https://www.mayoclinic.org/healthy-lifestyle/getting-pregnant/in-depth/hlv-20049462 (Accessed on 23 Sep 2019). 16. Clark L, et al. Fertil Steril. 2011; 96:49. 17. Chung PW, et al. HKMJ. 2017; 23(6): 556-561.