3. Endometriosis results from the dislocation of basal endometrium
The development of endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity is the theory most widely accepted. It has been corroborated by the finding that endometrial fragments are found in the pouch of Douglas, grow in culture and implant under various experimental conditions. Retrograde menstruation is a physiological phenomenon. Not all women, however with patent tubes acquire endometriosis. Recently, it was shown that eutopic endometrium shares alterations with the ectopic tissue that are not found in the eutopic endometrium of disease-free women. Therefore, the view has been advanced that the primary defect in endometriosis may be located in the eutopic endometrium of these. It was furthermore
suggested that endometriosis and adenomyosis are variants of the same disease process with uterine peristalsis and hyperperistalsis being important causal factors. It was proposed that adenomyosis would result from the infiltration of basal endometrium into myometrial dehiscencies that were caused by chronic uterine peristalsis and hyperperistalsis and that the muscular component of adenomyosis would result secondarily from metaplasia of the infiltrating endometrial stroma. It was furthermore suggested that endometriosis would result from the detachment of endometrial cells with a higher potential for proliferation and infiltrative growth and from their enhanced transtubal transport by uterine hyperperistalsis into the peritoneal cavity, where they implant on peritoneal surfaces.
At the end of the secretory phase and at the time of the onset of menstruation mitotic and hence proliferative activity, however, is only present in the basal layer of the primate endometrium, while in all of the functionalis and in the spongiosa mitotic quiescence prevails. Furthermore, peristromal smooth muscle cells have been shown to be present in peritoneal endometriotic lesions and that they may result from stromal metaplasia of the shed and implanted endometrium indicating that, with respect to the main morphological components, i.e. endometrial epithelium, endometrial stroma and smooth muscular tissue, no principal difference exists between endometriosis and adenomyosis. The production of smooth muscle cells by stromal metaplasia, however, constitutes, during organogenesis and in the adult, a potential that is confined to the basal endometrium at the endometrial myometrial junction. In view of these considerations the hypothesis was tested that both, adenomyosis and endometriosis, result from the dislocation of basal endometrium – adenomyosis by direct infiltration of basalis into the myometrial wall and endometriosis following the detachment of fragments of the basalis during menstruation and their transplantation into the peritoneal cavity.
Normal uteri and uteri with adenomyosis obtained by hysterectomy, excised endometriotic lesions and menstrual blood of women with and without endometriosis were used. Estrogen receptor (ER), progesterone receptor (PR), progesterone receptor B isoform (PRB)) and P450 aromatase (P450A) immunohistochemistry was performed with the use of specific monoclonal antibodies.
With respect to the parameters studied there was a fundamental difference between the cyclical patterns of the basalis and the functionalis of the eutopic endometrium. The endometrium of endometriotic and adenomyotic lesions mimicked the cyclical pattern of the basalis. The peristromal muscular tissue of endometriotic and adenomyotic lesions displayed the same cyclical pattern of ER and PR expression as the archimyometrium. There was a significantly higher prevalence of fragments of shed basalis in menstrual blood of women with endometriosis than in healthy controls.
In conclusion, the data add further support to our previous notion that endometriosis is, as adenomyosis, primarily a disease of the archimetra. There is strong circumstantial evidence that both endometriosis and adenomyosis are derived from the basal layer of the endometrium. Furthermore, it is proposed that dislocated basal endometrium has stem cell character capable of resuming embryonic growth potential and resulting in the ectopic formation of all archimetrial components such as epithelium, stroma and paramesonephric smooth muscle cells. In women with early onset endometriosis and adenomyosis the dislocation of the basal endometrium most probably results from auto-traumatisation by uterine hyperperistalsis as a dysfunction of the uterine mechanism of rapid sperm transport The biological mechanisms that govern normo- and hyperperistalsis, however, remain to be elucidated.
References
Leyendecker G, Herbertz M, Kunz G, Mall G.Endometriosis results from the dislocation of basal endometrium. Hum Reprod. 2002 Oct;17(10):2725-36.
Kunz G, Beil D, Huppert P, Leyendecker G. Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging. Hum Reprod. 2000 Jan;15(1):76-82.
Leyendecker G, Kunz G, Noe M, Herbertz M, Mall G.Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update. 1998 Sep-Oct;4(5):752-62.
Leyendecker G, Kunz G, Wildt L, Beil D, Deininger H.Uterine hyperperistalsis and dysperistalsis as dysfunctions of the mechanism of rapid sperm transport in patients with endometriosis and infertility. Hum Reprod. 1996 Jul;11(7):1542-51.
Kunz G, Beil D, Deininger H, Wildt L, Leyendecker G. The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod. 1993 Nov;8 Suppl 2:72-6.
4. Single embryo transfer
It has been recognized that multiple pregnancy and its obstetric, neonatal, developmental and financial consequences represent the main iatrogenic complication of IVF and ICSI. Several studies have shown that reducing the number of embryo transferred from a standard number of three to two, in patients who have several early cleaving stage embryos to chosse from, is not followed by a decrease of the overall ongoing pregnancy rate. It eliminates most triplets but does not decrease the rate of twin pregnancies.
In the first of two studies of the group published in the October 2002 issue of Human Reproduction data on the effect of elective single embryo transfer (eSET) on the total and multiple pregnancy rates of an IVF/ICSI programme are reported. A retrospective cohort analysis of eSET was carried out over a 4 year period. A total of 1559 cycles resulted in 1464 transfers; 299 transfers of one top quality embryo (20.4%) and 86 of one non-top quality embryo (5.9%) yielded 149 conceptions (49.8%) with 105 ongoing pregnancies (35.1%) and 26 conceptions (30.2%) with 19 ongoing implantations (22.1%) respectively; 1079 transfers of two (n = 853; 58.3%) or more than two (n = 226; 15.4%) embryos yielded 366 ongoing pregnancies (33.9%). The ongoing pregnancy rates for the years between 1998 and 2001 were 35.9, 27.9, 31.9 and 31.0% per oocyte retrieval and 38.5, 29.4, 34.1 and 33.2% per transfer. There were no differences in pregnancy rates between any of the years. The average ongoing pregnancy rate (>12 weeks) over the 4 years was 31.5% per started cycle and 33.5% per transfer; the average number of embryos transferred decreased from 2.26 (1998) to 1.79 (2001); the multiple pregnancy and twinning rates dropped from 33.6 and 29.5% (1998) to 18.6 and 16.3% (2001) respectively. It is concluded that judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate.
The aim of the other study was to evaluate the impact of transferring a single top quality embryo in the first IVF/ICSI cycle of patients <38 years old who chose to have one or two embryos transferred. A total of 262 patients participated in the study, and 243 transfers were performed: 156 (64%) patients chose the transfer of a single top quality embryo, if available, and two non-top quality embryos if not available; 87 (36%) patients chose to have a double embryo transfer regardless of embryo quality. In the first group an ongoing pregnancy rate of 40% (63/156) with a twin pregnancy rate of 2% (1/63) was achieved. In the second group the ongoing pregnancy rate was 44% (38/87) with 26% (10/38) twin pregnancies. In the patient group with only one embryo transferred, irrespective of the patient's choice, the ongoing pregnancy rate was 43% (54/127) with no twin pregnancies. For the study population as a whole, the ongoing pregnancy rate was 42% (101/243) with 11% (11/101) twins. It is concluded that the introduction of single embryo transfer in the first IVF/ICSI cycle is highly acceptable in women <38 years old
References
Gerris J, De Neubourg D, Mangelschots K, Van Royen E, Vercruyssen M, Barudy-Vasquez J, Valkenburg M, Ryckaert G.Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme. Hum Reprod. 2002 Oct;17(10):2626-31.
Impact of patients' choice for single embryo transfer of a top quality embryo versus double embryo transfer in the first IVF/ICSI cycle.Impact of patients' choice for single embryo transfer of a top quality embryo versus double embryo transfer in the first IVF/ICSI cycle.Hum Reprod. 2002 Oct;17(10):2621-5.
