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Newsletter No 18
  1. PCOS and ovarian drilling: endocrine and ultrasonographic outcomes.
  2. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin
  3. Endometriosis results from the dislocation of basal endometrium
  4. Single embryo transfer

1. PCOS and ovarian drilling: endocrine and ultrasonographic outcomes

There is considerable controversy as to how long the beneficial effects of laparoscopic ovarian drilling (LOD) last. The long-term clinical outcome was reported in the 17th newsletter. This follow-up study was undertaken to investigate the long-term effects of LOD. The study included 116 anovulatory women with polycystic ovary syndrome (PCOS) who underwent LOD between 1991 and 1999 (study group) and 34 anovulatory PCOS women diagnosed during the same period, who had not undergone LOD (comparison group). The hospital records were reviewed and most patients attended for a transvaginal ultrasound scan and blood sampling to measure the serum concentrations of LH, FSH, testosterone, androstenedione and sex hormone-binding globulin. The results before and at different intervals, short- (<1 year), medium- (1-3 years) and long-term (4-9 years), after LOD were compared. The LH:FSH ratio, mean serum concentrations of LH and testosterone and free androgen index decreased significantly after LOD and remained low during the medium- and long-term follow-up periods. The mean ovarian volume decreased significantly (P < 0.05) from 11 ml before LOD to 8.5 ml at medium-term and remained low (8.4 ml) at long-term follow-up. The beneficial endocrinological and morphological effects of LOD appear to be sustained for up to 9 years in most patients with PCOS.


Amer SA, Gopalan V, Li TC, Ledger WL, Cooke ID. Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome. Hum Reprod. 2002 Aug;17(8):2035-42.

Amer SA, Banu Z, Li TC, Cooke ID.Long-term follow-up of patients with polycystic ovary syndrome after laparoscopic ovarian drilling: endocrine and ultrasonographic outcomes. Hum Reprod. 2002 Nov;17(11):2851-7.

2. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin

In this study it was determined whether metformin, which had facilitated conception in 72 oligoamenorrhoeic women with polycystic ovary syndrome (PCOS), would safely reduce the rate of first trimester spontaneous abortion (SAB) and increase the number of live births without teratogenicity.

Seventy-two oligoamenorrhoeic women with PCOS conceived on metformin (2.55 g/day). They were prospectively assessed in an outpatient clinical research centre. Outcome measures included number of first trimester SAB, live births, normal ongoing pregnancies >/=13 weeks, gestational diabetes (GD), congenital defects (CD), birth weight and height, as well as weight, height, and motor and social development during the first 6 months of life.

Of the 84 fetuses, to date there have been 63 normal live births without CD (75%), 14 first trimester SAB (17%), and seven ongoing pregnancies >/=13 weeks with normal sonograms without CD (8%). Previously, without metformin, 40 of the 72 women had 100 pregnancies (100 fetuses) with 34 (34%) live births and 62 (62%) first trimester SAB. In current pregnancies on metformin in these 40 women (46 pregnancies, 47 fetuses), there have been 33 live births (70%), two pregnancies ongoing >/=13 weeks (4%), and 12 SAB (26%) (P < 0.0001). There was no maternal lactic acidosis, and no maternal or neonatal hypoglycaemia. Fasting entry serum insulin was a significant explanatory variable for total (previous and current) first trimester SAB, odds ratio 1.32 (for each 5 micro U/ml rise in insulin), 95% CI 1.09-1.60 (P = 0.005). On metformin, GD developed in 4% of pregnancies versus 26% of previous pregnancies without metformin, P = 0.025. There have been no major CD in the 63 live births or CD by sonography in the seven fetuses Reference

Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod. 2002 Nov;17(11):2858-64.

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.


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


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.

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Gerhard Leyendecker