Should we offer fertility preservation to all patients with severe endometriosis? Daniel S. Seidman, MD Department of Ob/Gyn, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University
Endometriosis and infertility What is the long term impact of endometriosis on fertility? Should we offer fertility preservation?
Endometriosis Epidemiology Globally 90 million suffering with Endometriosis Prevalence is similar in all races Peak incidence: 30-45 yrs of age
Non-growing follicles Human Follicle count representing the reserve of the ovary 1,000,000 100,000 Endometriosis 10,000 1,000 100 Ovarian failure Low reserve POF Age related infertility 10 20 30 40 50 Age to menopause Adapted from Wallace Kelsey 2010
Methods A total of 126 patients operated on for bilateral ovarian endometriosis All aged < 40 yrs Mean + SD age 30.4 + 4.3 years.
Results Postsurgical ovarian failure was documented in 3 cases A rate of 2.4% (95% CI 0.5%-6.8%). In all cases, this complication occurred immediately after surgery.
Results All affected women reported regular menstrual cycle before the intervention, and ovarian failure occurred immediately after surgery in all the women. The study indicated that the complication is strictly consequent to surgery. Patients who are operated on for bilateral endometriomas should be informed that they have a low, but definite, risk of POF occurring immediately after surgery.
Age at menopause (years)
Conclusions Patients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.
Methods Analyzed data for 24,153 pre- and postmenopausal women who were enrolled in the Japan Nurses Health Study (JNHS) at the ages 40 59 years. The main outcome measure was menopause.
Results
Results
Results
Conclusions Menopause in women who have a past history of infertility, especially in those who have suffered from endometriosis, is significantly earlier than that in women without such a history.
Should we offer young women with endometriosis fertility preservation techniques?
Different approaches for fertility preservation Currently used & experimental Primordial follicles Early growth Mature eggs Stored ovarian tissue Ovarian tissue transplantation Follicle maturation (Not practiced) In-vitro Egg maturation Mature egg or embryo freezing
Single procedure- IVM + Ovarian tissue Fluid with immature eggs immature egg collection IVM Ovarian tissue cryopreservation Embryo cryopreservation
Cryopreservation of oocytes
Function of frozen / thawed ovarian tissue after transplantation ovary Site Cases 21/25 Ovarian function Menstruation / Hormonal Ovulation Denmark Rigs hospitalet 100% peritoneum 9/25 + ovary + 21/22 Spain La Fe 94% peritoneum 8/22 + Russia Ava- Peter arm abdomen ovary 4/17 11/17 8/13 76% Belgium St Luc 77% peritoneum 7/13 + Israel Sheba Ovary + 10/10 100% + + No No + + AMH not predictive usually low Janse F. et.al. Endoc. Res. 2011 Endocrine function most of patients years Andersen CY et.al. RBM Online 2012
Ovarian transplantation results - Sheba Age Diagnosis Transp. Endocrine IVF Pregnancy SH 33 B cell Lymph. 02/2004 2 years + ++ AG 36 Hodgkin s 02/2010 + + GN 42 B cell Lymph. 02/2010 6 mo. + BH 27 Hodgkin s d. 02/2010 + + + + (s) TM 27 CML 07/2010 09/2011 1 year + + RA 23 Hodgkin s d. 03/2011 + ++(s) CS 31 Hodgkin s d. 07/2011 + FR 45 Breast Ca. 12/2012 + BHR 22 Ewing Sarcoma 11/2012 Single transplantation 3 years activity, 3 pregnancies
Ovarian transplantation results - Sheba Spontaneous menstruation returned in all patients AMH FSH & E2 not predictive Long term graft survival in most patients IVF cycles -modified natural protocol in all cycles Empty follicles only a few after first cycles No. of embryos post transplantation HIGHER than No. of embryos stored prior to chemotherapy Cryopreservation/transplantation of ovarian tissue works and is effective
Ovarian cortex cryopreservation should be proposed to all women at high risk of severe recurrent ovarian endometriomas.
Orthotopic transplantation of fresh ovarian cortex: laparoscopic procedure
Ovarian tissue was reimplanted onto the remaining ovary after removal of the native cortex.
At second look laparoscopy
Conclusions In moderate and severe endometriosis, a medico-surgical approach remains the gold standard. Very frequently, normal ovarian tissue is excised together with the endometrioma wall. Ovarian surgery in endometriosis patients should therefore be performed by experienced surgeons in order to both preserve and improve fertility.
Conclusions A low ovarian reserve after laparoscopic cystectomy for endometriomas is not rare. Preservation of ovarian tissue should be considered in all patients at serious risk of future fertility impairment, particularly before any treatment likely to result in ovarian endometriosis recurrence and/or premature ovarian failure.
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