1. Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging.
   
2. Endocrine disruptors and endometriosis/adenomyosis.
   
3. Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates.
   
4. Anastrazole and oral contraceptives: a novel treatment for endometriosis.
   

1. Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging.

The hypothesis is tested that there is a strong association between endometriosis and adenomyosis and that adenomyosis plays a role in causing infertility in women with endometriosis. Magnetic resonance imaging of the uteri was performed in 160 women with and 67 women without endometriosis. The findings were correlated with the stage of the disease, the age of the women and the sperm count parameters of the respective partners. The posterior junctional zone (PJZ) was significantly thicker in women with endometriosis than in those without the disease (P<0.001). There was a positive correlation of the diameter of the PJZ with the stage of the disease and the age of the patients. The PJZ was thicker in patients with endometriosis with fertile than in patients with subfertile partners. The prevalence of adenomyotic lesions in all 160 women with endometriosis was 79%. In women with endometriosis below an age of 36 years and fertile partners, the prevalence of adenomyosis was 90% (P<0.01) It is concluded that with a prevalence of up to 90%, uterine adenomyosis is significantly associated with pelvic endometriosis and constitutes an important factor of sterility in endometriosis presumably by impairing uterine sperm transport. Other, ‘non-mechanical’ effects of adenomyosis are also discusses such as the direct effect of the adenomyotic lesions on ovarian function via the utero-ovarian counter-current system (see also Kuivasaari et al., 2005; this newsletter). The common cause of the development of adenomyosis/endometriosis is viewed in uterine peristaltic activity and particularly hyper- and dysperistalsis based on archimetral hyperoestrogenism that may have various, not yet fully elucidated etiologies. One of these might consist in the effects of endocrine disruptors that may not only be effective within the archimetra but also in the endometriotic/adenomyotic lesions (see also Heilier et al., 2005; this newsletter).

References

Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. Adenomyosis in endometriosis--prevalence and impact on fertility. Evidence from magnetic resonance imaging. Hum Reprod. 2005 Aug;20(8):2309-16.

Leyendecker G, Kunz G, Herbertz M, Beil D, Huppert P, Mall G, Kissler S, Noe M, Wildt L. Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci. 2004 Dec;1034:338-55

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2. Increased dioxin-like compounds in the serum of women with peritoneal endometriosis and deep endometriotic (adenomyotic) nodules.

In a case-control study, involving seventy-one women with peritoneal endometriosis (n = 25) or deep endometriotic (adenomyotic) nodules (n = 25) and controls (n = 21), the possible association between the body burden of dioxin-like compounds and endometriotic disease was investigated. INTERVENTION(S): Collection of 200 mL of blood (fasted) and face-to-face interview. Dioxin (PCDD), furan (PCDF), and dioxin-like PCB serum concentrations (picograms toxic equivalent [TEQ]/g lipids) were assessed. Age and body mass index were traced by linear multiple regression as determinants of total TEQ levels. After standardization for these variables (30 years and 22.5 kg/m2), the mean TEQ levels were 24.21 (controls), 30.62 (peritoneal endometriosis), and 37.60 (deep endometriotic [adenomyotic] nodules) pg TEQ/g lipids. Logistic regression analysis indicated a significantly increased risk of deep endometriotic (adenomyotic) nodules (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4-7.6) for an increment of 10 pg in total TEQ levels/g lipids. An increased risk was also found for peritoneal endometriosis (OR, 1.9; 95% CI, 0.9-3.8) for total TEQ levels and for dioxins alone (OR, 3.2; 95% CI, 1.0-9.9). The results provide the first epidemiological evidence of an association between increased PCDD/PCDF and PCB body burden and endometriosis.

Reference

Heilier JF, Nackers F, Verougstraete V, Tonglet R, Lison D, Donnez J. Increased dioxin-like compounds in the serum of women with peritoneal endometriosis and deep endometriotic (adenomyotic) nodules. Fertil Steril. 2005 Aug;84(2):305-12.

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3. Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates.

Women with endometriosis often need IVF to conceive--most women need several cycles of treatment. To evaluate the impact of moderate to severe endometriosis on cumulative IVF outcome, an observational study was carried out on 98 consecutive women who underwent IVF or ICSI treatment and had endometriosis diagnosed by laparoscopy or laparotomy and classified as minimal to mild endometriosis (American Society for Reproductive Medicine I/II) (n = 31) or moderate to severe endometriosis (American Society for Reproductive Medicine) III/IV) (n = 67). The reference group consisted of 87 consecutive women with tubal infertility. The main outcome measures were cumulative pregnancy and live birth rates. There was a significantly lower pregnancy rate per fresh embryo transfer after pooled cycles (1-4) among women with stage III/IV endometriosis (22.6%) compared to stage I/II group (40.0%) or tubal infertility (36.6%). After 1-4 IVF/ICSI treatments, including frozen embryo transfer, 56.7% of the women with stage III/IV endometriosis were pregnant and 40.3% gave birth. The corresponding values were 67.7/55.8% when endometriosis was stage I/II and 81.6/43.7% in the controls respectively. It is concluded that stage III/IV endometriosis means a worse prognosis for IVF/ICSI treatments compared to milder stages or tubal factors. Lower implantation and multiple pregnancy rates offer some support to our practice to continue two embryo transfers in this group.

Reference

Kuivasaari P, Hippelainen M, Anttila M, Heinonen S. Effect of endometriosis on IVF/ICSI outcome: stage III/IV endometriosis worsens cumulative pregnancy and live-born rates. Hum Reprod. 2005 Jul 8;

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4. Anastrazole and oral contraceptives: a novel treatment for endometriosis.

This prospective open-label Food and Drug Administration phase 2 trial with Institutional Review Board approval study was performed to establish the use of aromatase inhibitors as a therapeutic option for endometriosis. Fifteen premenopausal patients with documented refractory endometriosis and chronic pelvic pain were included in the study. After a 1-month washout of endometriosis hormone therapies, women took 1 mg anastrazole (Arimidex; AstraZeneca, Wilmington, DE) and one tablet of 20 microg ethinyl estradiol/0.1 mg levonorgestrel (Alesse; Wyeth, Madison, NJ) daily for 6 months. An analog pain scale recorded pelvic pain in daily diaries and surveys at baseline and after each treatment month. Side effects, blood counts, liver and renal function tests, cholesterol levels, and bone density were monitored. Fourteen of 15 patients achieved significant pain reduction. Median pain scores decreased 55% after 6 months, while mean pain scores decreased 40%. Pain reduction comparing each treatment month to baseline achieved statistical significance. Average pain scores began dropping after only 1 treatment month and continued decreasing each additional month. No organ system experienced adverse effects. Estradiol levels were suppressed during treatment. Side effects were mild and improved over time. It is concluded that fourteen of 15 patients with refractory endometriosis achieved significant pain relief using anastrazole and 20 microg ethinyl estradiol/0.1 mg levonorgestrel with minimal side effects. This treatment for endometriosis is a promising new modality that warrants further investigation.

Reference

Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin SD, Bulun SE Anastrazole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril. 2005 Aug;84(2):300-4.

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