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11 EFFECT OF LAPAROSCOPIC SURGERY ON OVARIAN FUNCTION IN WOMEN WITH ENDOMETRIOSIS
Innovations in Assisted Reproductive Technologies alterations may explain the variety of generalized symptoms and systemic changes reported by affected women. Increased levels of inflammatory cytokines, growth factors, and prostaglandins in the peripheral blood and peritoneal fluid and markedly elevated production of these substances by peripheral blood monocytes and peritoneal macrophages, may be responsible for low-grade fever, malaise, prostration, fatigue, nausea, vomiting, diarrhea, and chronic aches and pains variable in character, intensity, and location. Recently, immunohistochemical studies from separate laboratories demonstrated the presence of nerve fibers and nerve growth factors (NGF) in the ectopic endometrium but more interestingly, also in the uterine endometrium of affected women. The presence of sensory, adrenergic, and cholinergic nerve fibers in eutopic endometrium appears to be substantially increased in women with endometriosis compared to those without the disease It is quite likely that these nerve fibers transmit pain stimuli from the uterus as well as from endometriotic implants, and out of the pelvis through neural ganglia including the stellate ganglion located in the neck to the Central Nervous System (CNS). A decrease in the concentration of these nerve fibers was demonstrated after treatment of endometriosis and in association with symptomatic improvement. In experimental studies, activated macrophages, macrophage-conditioned media, or TNF-a stimulate neurite outgrowth and induce NGFs in astrocytes which express TNF-R1 and TNF-R2. This is consistent with our own reports of increased concentrations of activated monocytes/macrophages and increased synthesis of TNF-a in endometriosis (Braun, et al. 1996). Increased CNS levels of NGF and other neural growth factors have been associated with clinical depression common to endometriosis and Chronic Pain Syndromes. Taken together, these findings have lead us to hypothesize a causal relationship between immunologic factors known to be abnormal in endometriosis, nerve growth factor abnormalities recently described in eutopic and ectopic endometrium, and the clinical symptomatology of this disease. Furthermore, because the stellate ganglion block (SGB) has been shown to be beneficial in Post-Traumatic Stress Disorder and in Chronic Visceral Pain Syndromes, we further postulated that this procedure might also produce clinically significant effects in endometriosis. To evaluate this hypothesis, we performed SGB in a pilot study involving four women with Chronic Pelvic Pain Syndrome associated with pelvic endometriosis. All seemed to have a significant symptomatic improvement lasting for 3 4 months after 1 or 2 SGBs. A prospective clinical trial is currently underway. 11 EFFECT OF LAPAROSCOPIC SURGERY ON OVARIAN FUNCTION IN WOMEN WITH ENDOMETRIOSIS W.P. Dmowski, N. Rana, J. Ding. Institute for the Study & Treatment of Endometriosis, Oak Brook, USA Ovarian cystectomy and resection/stripping of the endometrioma capsule is a routine laparoscopic procedure in women with advanced endometriosis. However, ovarian follicles have been identified in resected specimens (Hachisuga and Kawarabayashi 2002, and Muzii, et al 2002) and after cystectomy, a decrease in ovarian arterial blood flow and a transient rise in FSH levels have been reported which suggest a decrease in the ovarian reserve. Post-cystectomy response to ovarian stimulation was reduced (Loh, et al. 1999) as was the number of follicles and eggs retrieved (Ho, et al 2002). For this reason, fenestration/coagulation rather than resection were suggested but the recurrence rates were higher than post-cystectomy. More recently, Donnez, et al (2010) recommended a combined cystectomy and ablation approach.
S5 To evaluate the effect of endometrioma resection on subsequent ovarian reserve, we compared ovarian response to stimulation during IVF cycles performed after laparoscopic: (1) Ablation of superficial ovarian endometriosis [Group 1]; (2) Resection of ovarian endometriomas with stripping of the endometrioma capsule [Group 2]; and (3) Resection of uterine leiomyomas [Group 3]. We reviewed 856 consecutive IVF cycles: 62 of these were performed in 46 women after laser ablation of ovarian endometriosis, 47 in 36 women after resection of ovarian endometriomas, and 18 in 18 women following resection of uterine leiomyomas. Ovarian tissue-sparing techniques were used in all cases. There was no difference between the groups in day 3 FSH levels before or after surgery. There was, however, high variability related to women’s age and ovarian reserve. In Group 2, day 3 FSH level was higher following endometrioma resection (p < 0.05). There was no difference in the response to stimulation between the groups in the gonadotropin dose, number of oocytes aspirated, mean estradiol levels at hCG administration, mean number of transferable embryos, and pregnancy and implantation rates. However, when the patients were age-matched, the response to stimulation was lower in the endometrioma group but pregnancy and implantation rates were similar for all groups. In patients of Group 2 who had unilateral endometriomas resected, we also compared the number of developing follicles greater than or equal to 14 mm in resected and non-resected ovaries. There were no differences if endometriomas were less than 3 cm in diameter. However, following resection of endometriomas 3 cm and greater, the mean number of developing follicles in that ovary was only 3.3 as compared to 5.9 follicles in the non-resected contralateral ovary (p < 0.02). We conclude that resection of ovarian endometriomas, especially those larger than 3 cm, may have adverse effect on ovarian reserve and may decrease the response of that ovary to subsequent stimulation. However, the possibility that large endometriomas by themselves may adversely affect the ovarian reserve needs to be considered and is suggested by elevated day 3 FSH levels even before surgery. 12 THE IMPACT OF THE BLOCKADE OF DNA METHYLATION ON THE ENDOMETRIAL ECTOPIES IN THE CONDITIONS OF LABORATORY MODEL V.V. Evdokimova. Odessa State Medical University, Odessa, Ukraine Endometriosis is the complex disease characterizing with the pathological and compensatory changes in the affected organs and tissues, with the general disorders in the female organism as the response to the local lesions with ectopic endometrium. This dishormonal, immunodependent and genetically predetermined disease takes the third place in the structure of gynecological morbidity and occurs in 8 15% females of fertile age. Accordingly to the data of recent researches the incidence of endometriosis is 17% for primary health care and 30% for patients requiring surgery. There are widely used laboratory models when the new methods of the diagnosis and treatment are implementing to the medical practice. To assess the growth dynamics of endometrial ectopies in the conditions of the various activity of DNA methylation there was conducted the experimental study. The sample size was 80 Wistar rats distributed into the referent groups: control group (n = 20) with intact animals; I experimental animals (n = 30) animals with the artificially modeled endometriosis, animals with the modeled II experimental animals (n = 30) endometriosis and the blockade of DNA methylation with 5-aza2-deoxycytidine (SigmaChemical Co., USA). The duration of the experiment was 3 weeks. For modeling endometriosis there
S5 To evaluate the effect of endometrioma resection on subsequent ovarian reserve, we compared ovarian response to stimulation during IVF cycles performed after laparoscopic: (1) Ablation of superficial ovarian endometriosis [Group 1]; (2) Resection of ovarian endometriomas with stripping of the endometrioma capsule [Group 2]; and (3) Resection of uterine leiomyomas [Group 3]. We reviewed 856 consecutive IVF cycles: 62 of these were performed in 46 women after laser ablation of ovarian endometriosis, 47 in 36 women after resection of ovarian endometriomas, and 18 in 18 women following resection of uterine leiomyomas. Ovarian tissue-sparing techniques were used in all cases. There was no difference between the groups in day 3 FSH levels before or after surgery. There was, however, high variability related to women’s age and ovarian reserve. In Group 2, day 3 FSH level was higher following endometrioma resection (p < 0.05). There was no difference in the response to stimulation between the groups in the gonadotropin dose, number of oocytes aspirated, mean estradiol levels at hCG administration, mean number of transferable embryos, and pregnancy and implantation rates. However, when the patients were age-matched, the response to stimulation was lower in the endometrioma group but pregnancy and implantation rates were similar for all groups. In patients of Group 2 who had unilateral endometriomas resected, we also compared the number of developing follicles greater than or equal to 14 mm in resected and non-resected ovaries. There were no differences if endometriomas were less than 3 cm in diameter. However, following resection of endometriomas 3 cm and greater, the mean number of developing follicles in that ovary was only 3.3 as compared to 5.9 follicles in the non-resected contralateral ovary (p < 0.02). We conclude that resection of ovarian endometriomas, especially those larger than 3 cm, may have adverse effect on ovarian reserve and may decrease the response of that ovary to subsequent stimulation. However, the possibility that large endometriomas by themselves may adversely affect the ovarian reserve needs to be considered and is suggested by elevated day 3 FSH levels even before surgery. 12 THE IMPACT OF THE BLOCKADE OF DNA METHYLATION ON THE ENDOMETRIAL ECTOPIES IN THE CONDITIONS OF LABORATORY MODEL V.V. Evdokimova. Odessa State Medical University, Odessa, Ukraine Endometriosis is the complex disease characterizing with the pathological and compensatory changes in the affected organs and tissues, with the general disorders in the female organism as the response to the local lesions with ectopic endometrium. This dishormonal, immunodependent and genetically predetermined disease takes the third place in the structure of gynecological morbidity and occurs in 8 15% females of fertile age. Accordingly to the data of recent researches the incidence of endometriosis is 17% for primary health care and 30% for patients requiring surgery. There are widely used laboratory models when the new methods of the diagnosis and treatment are implementing to the medical practice. To assess the growth dynamics of endometrial ectopies in the conditions of the various activity of DNA methylation there was conducted the experimental study. The sample size was 80 Wistar rats distributed into the referent groups: control group (n = 20) with intact animals; I experimental animals (n = 30) animals with the artificially modeled endometriosis, animals with the modeled II experimental animals (n = 30) endometriosis and the blockade of DNA methylation with 5-aza2-deoxycytidine (SigmaChemical Co., USA). The duration of the experiment was 3 weeks. For modeling endometriosis there