In-vitro ovarian steroidogenesis in women with pelvic congestion

C. Gilling-Smith1, H. Mason, D. Willis, S. Franks and R.W. Beard

Department of Obstetrics and Gynaecology, Imperial College School of Medicine at St Mary's, London W2 1PG, UK


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Follicular fluid steroid content and theca and granulosa cell steroidogenesis in pelvic congestion cystic ovaries were compared with steroidogenic function in both normal and polycystic ovaries. Ovaries were obtained at oophorectomy for benign gynaecological conditions, and classified according to gross morphology at dissection. Individual follicles were dissected out, follicular fluid aspirated, and granulosa and theca cells cultured in vitro. Androstenedione, progesterone and oestradiol content of the follicular fluid and overlying culture medium were measured by radioimmunoassay. There was a significant elevation of both basal and LH-stimulated androstenedione production by theca from both polycystic ovaries (n = 10; P < 0.005) and pelvic congestion cystic ovaries (n = 8; P < 0.05 and < 0.01 respectively) as compared with normal ovaries (n = 5). Granulosa cells from pelvic congestion ovaries (n = 7) had a diminished oestradiol response to FSH as compared with those from normal ovaries (n = 8). Follicular fluid from the majority of follicles in the pelvic congestion cystic ovaries had a high androgen:oestrogen ratio consistent with atresia. For the first time, pelvic congestion ovaries characterized by predominantly atretic follicles scattered throughout the stroma in a normal volume ovary are reported. Follicular atresia was reflected by reduced granulosa cell responsiveness to FSH, theca cell hyperplasia and increased basal and LH-stimulated androgen production. These ovaries are functionally distinct from polycystic ovaries, which do not have a higher proportion of atretic follicles than normal ovaries.

Key words: human granulosa/human theca/ovarian morphology/ovarian steroids/pelvic congestion


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Pelvic congestion is the commonest cause of chronic pelvic pain in women of reproductive age (Beard et al., 1984Go). Diagnosis is based on clinical history and the triad of negative laparoscopy, reduced venous clearance and engorgement at transuterine venography (Beard et al., 1984Go) and evidence of dilated pelvic veins and reduced Doppler blood flow on ultrasound (Stones et al., 1990Go).

The causal relationship between venous stasis and chronic pain is unknown. However, several lines of evidence suggest that ovarian hormones may play a central role in pathogenesis. The condition is found exclusively in women of reproductive age (Taylor, 1954Go; Beard et al., 1988Go; Steege, 1993). Suppression of cyclical ovarian activity, either medically (Reginald et al., 1989Go; Farquhar et al., 1989Go) or following bilateral oophorectomy (Beard et al., 1991Go; Reid and Gangar, 1994Go), produces a significant reduction in both venous stasis and chronic pain. In animal studies, changes in uterine blood flow have been noted just before and during oestrus (or ovulation) and during the luteal phase (Greiss and Anderson, 1969Go). This may be either a direct effect of oestrogen on the pelvic vasculature (Greiss and Anderson, 1970Go) or mediated through the release of prostaglandins and/or nitric oxide (Van Buren et al., 1992Go). In the human ovary, where data are limited, selective ovarian vein dilatation has been noted on the side of the developing follicle and venous dilatation increases during the follicular phase to peak at the time of ovulation (Reginald et al., 1986Go). In some preliminary studies, no significant differences were found in peripheral gonadotrophins, ovarian steroid concentrations or gonadotrophin pulsatility in women with pelvic congestion compared with asymptomatic controls, matched for ovarian morphology—an observation which weakens the putative link between ovarian hormones and congestion.

An alternative view is that pelvic congestion arises as a result of localized disturbances in ovarian steroid output. The ideal test of this hypothesis would be to take blood samples from the ovarian vein, in both control and affected women, precisely timed according to day of cycle. Such a study has huge practical limitations. An alternative, but more feasible approach is to study ovarian morphology and steroidogenic function in these women. Women with pelvic congestion have been found to have an increased incidence of abnormal ovarian morphology compared with normal controls (Taylor, 1949Go; Adams et al., 1990Go). Using ultrasound as a primary means of defining morphology, it was found (Adams et al., 1990Go) that over 50% of women with pelvic congestion had cystic changes in their ovaries. These ovaries fell into two morphologically distinct groups. The first showed the classic polycystic ovary pattern of increased ovarian volume and stroma, with a peripheral distribution of 10 or more small follicles between 2 and 8 mm in diameter. The second were of normal volume, but contained clusters of larger follicles dispersed throughout the stroma and were quite distinct from multicystic ovaries, typically associated with weight loss-related amenorrhoea, in which ovarian and uterine volume are reduced (Adams et al., 1985Go). In a parallel morphological study of ovaries removed from women at hysterectomy for chronic pain due to pelvic congestion, two types of ovaries with cystic changes were similarly identified. The first had the classic polycystic ovary characteristics described above, while the second were clearly distinct from both normal and polycystic ovaries by the presence of numerous follicles, 7–11 mm in diameter throughout a stroma which was of normal density. The latter ovarian morphology has not been previously reported and, since they were only identified in women with pelvic congestion, they are referred to in the present report as pelvic congestion cystic. In the present series of 61 patents undergoing oophorectomy for pelvic congestion, 43% had normal ovaries, 26% had polycystic ovaries, and 23% had pelvic congestion cystic ovaries (C.Gilling-Smith and H.Mason, unpublished observations).

In order to explore the hypothesis that a localized disturbance in ovarian steroids may be central to the aetiology of pelvic congestion, in-vitro theca and granulosa cell steroidogenesis and follicular fluid steroid content were compared in three groups of ovaries removed at hysterectomy: normal, polycystic and pelvic congestion cystic. The principal aim was to identify any significant differences in the steroid output of the follicles in the polycystic and pelvic congestion cystic ovaries, as compared with normal ovaries. A further aim was to characterize, for the first time, the endocrine function of the morphologically distinct pelvic congestion ovary.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Patients
The study received approval from the Kensington, Chelsea and Westminster Health Authority Ethics Committee. Ovaries were obtained from women undergoing unilateral or bilateral oophorectomy for benign, non-ovarian gynaecological disease following informed consent. All hormonal medication was stopped at least 3 months before surgery. Note was made of the patient's age, menstrual cycle history, day of cycle at the time of oophorectomy, preoperative ultrasound findings, ovulatory status if previously determined, and the indication for surgery. Pelvic congestion was defined on the previously published criteria of negative laparoscopy, dilated veins on ultrasound (Stones et al., 1990Go) and congestion on transuterine venography (Beard et al., 1984Go).

Ovarian dissection
A central section was taken from each ovary for histopathological examination, and the remaining tissue placed in Hanks' balanced salt solution (HBSS) without calcium and magnesium (Gibco BRL, Paisley, UK) for transport to the laboratory and subsequent dissection. Individual follicles were dissected intact from the surrounding ovarian stroma under microscopic vision. Only follicles which appeared healthy were studied, i.e. well-vascularized and yielding translucent, pale yellow follicular fluid. The diameter of each follicle was measured with callipers, and the follicular fluid aspirated using a microsyringe. The follicular fluid was stored at –20°C before measurement of steroids by radioimmunoassay. The follicles were incised and the granulosa cells carefully scraped from the lamina basalis. The theca interna was then peeled from the base of the follicle. Ovarian morphology was defined at dissection according to previously published criteria (Gilling-Smith et al., 1994Go; Mason et al., 1994Go). Ovaries were defined as polycystic if they had at least three of the following four histological features: 10 or more follicles, typically 2–8 mm in diameter, distributed peripherally in any given cross-section; increased density and amount of ovarian stroma; increased ovarian volume (>9 ml); and thickened tunica (Gilling-Smith et al., 1994Go). Ovaries were defined as normal if their volume was <9 ml, there was no evidence of increased quantity and density of stroma, and only one or two follicles could be identified in any given section of the ovary. Criteria for defining an ovary as pelvic congestion cystic at dissection were based on previously published ultrasound data (Adams et al., 1990Go) and absence of features characterizing either the normal or polycystic ovary, i.e. evidence of larger follicles (4–12 mm) distributed in clusters of three to five cysts throughout the ovarian stroma, in ovaries which were of normal volume, had normal stromal density, and no thickening of the tunica.

Theca cell studies
Theca cells were isolated and cultured as previously described (Gilling-Smith et al., 1994Go). Following enzymatic dispersion, the cells were plated at a density of 10–15x104 cells per well in 24 mmx15 mm multi-well plates (Cel cult, Bibby Sterilin, Staffordshire, UK) and incubated in 1 ml serum-free culture medium comprising Medium 199 [(Earle's modified salts with L-glutamine, without phenol red, with extra L-glutamine (0.6 mg/ml), penicillin and streptomycin (50 IU/ml) (all from Gibco BRL)]. Highly purified human pituitary LH (donated by Dr Sé Lynch, Endocrine Services, Bidford-on-Avon, Warwickshire, UK; LH activity 12 700 IU/mg); FSH 7.0 IU/mg; thyroid-stimulating hormone (TSH) 6.5 mIU/mg was added to half the wells at a dose of 2.5 ng/ml (maximum effective dose) at the start of the incubation period. Since theca cell steroid production is increased in large follicles (Gilling-Smith et al., 1994Go), only theca from small follicles (<=10 mm diameter) was used. All experiments were performed in duplicate or triplicate wells. No substrate was added, and steroid accumulation over 48 h under basal and LH-stimulated conditions was measured. At the end of the culture period, the overlying medium was collected for radioimmunoassay of progesterone, androstenedione and oestradiol content.

Granulosa cell studies
Granulosa cell cultures were performed as previously described (Mason et al., 1994Go). Cells were pooled from all follicles containing clear follicular fluid. To allow for meaningful comparisons, all follicles of diameter >11 mm were excluded (Mason et al., 1994Go). Approximately 5x104 viable cells/well were incubated in a 200 µl volume of serum-free Medium 199 (Gibco BRL) with the addition of antibiotics (penicillin and streptomycin; Gibco) and 200 mmol/l L-glutamine. Incubations were carried out with the addition of 10–7 mol/l testosterone (Sigma Chemical Co., Poole, UK) as an aromatase substrate, and a range of doses of highly purified human FSH [<16 IU LH (16/40)/mg; kindly supplied by Dr S.Lynch]. All experiments were performed in triplicate wells. Medium was collected after a 48 h incubation period for measurement of oestradiol.

Radioimmunoassay
Androstenedione, progesterone and oestradiol in the stored incubation medium were measured by direct radioimmunoassay of the unextracted culture medium using antibodies and antisera as described previously (Gilling-Smith et al., 1994Go). Follicular fluid steroids were measured in all follicles containing clear fluid and assayed at dilutions of 1:10 to 1:1000. Parallelism was demonstrated with the standard curve across this range.

Statistical analysis
Theca cell steroid accumulation is expressed as mean (± SEM) pmol steroid/103 viable cells/48 h of culture unless otherwise stated. As the data were not normally distributed, comparison of steroid production between the three types of ovary was made using the Mann–Whitney U-test. Granulosa cell responses are expressed in pmol oestradiol/ 103 cells/48 h, and shown as the mean (± SE) of triplicate estimations from each ovary. Cumulative data of FSH dose–responses was analysed using two-way analysis of variance.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
Theca cell studies
Theca cell cultures were performed on 23 pairs of ovaries removed at oophorectomy. Pelvic congestion was the primary indication for surgery in all women with pelvic congestion cystic ovary morphology (n = 8), but only 20% of those with normal ovaries (n = 5) and 50% of those with polycystic ovaries (n = 10). Clinical details for the women with pelvic congestion cystic ovaries are shown in Table IGo. Five of the 10 women with polycystic ovaries, and all of those with pelvic congestion cystic ovaries, had regular ovulatory cycles and no clinical evidence of hyperandrogenism. Median basal and LH-stimulated progesterone, androstenedione and oestradiol production by theca cells from the three morphologically distinct types of ovary are shown in Table IIGo, and individual data points for progesterone, androstenedione and oestradiol production are shown in Figure 1Go. In the polycystic ovary theca, median basal and LH-stimulated androstenedione and progesterone production were both significantly elevated compared with the normal theca (P < 0.005 and < 0.05 respectively). This increase was particularly marked in the case of androstenedione, where there was no overlap in values with normal theca. A significant elevation of basal and LH-stimulated androstenedione production was also noted in the pelvic congestion cystic ovary theca compared with normal theca (P < 0.05 and < 0.01 respectively), although progesterone and oestradiol production were not significantly different. There were no statistically significant differences in progesterone, androstenedione and oestradiol steroidogenesis between polycystic and pelvic congestion cystic theca cells. The magnitude of response to LH in all three types of theca was similar (median 1.8-fold).


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Table I. Theca cell studies. Clinical spectrum of the eight women with pelvic congestion cystic ovaries
 

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Table II. Theca cell studies. Median (range) progesterone, androstenedione and oestradiol production (pmol/103 theca cells/48 h of culture) according to ovarian morphology at dissection
 




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Figure 1. Comparison of (A) androstenedione, (B) progesterone and (C) oestradiol accumulation in theca from five normal ovaries ({square}), ten polycystic ovaries (•) and eight pelvic congestion cystic ovaries ({blacktriangleup}) under basal and LH-stimulated conditions during the first 48 h of culture. Each data point represents the mean of duplicate or triplicate experiments. Plating density was 10–15x104 cells per well, and all other variables affecting magnitude of steroid production were kept constant. Note the log scale for magnitude of androstenedione production. See Table IIGo for median values and statistical significance data.

 
Granulosa cell studies
Granulosa cell cultures were performed on 22 pairs of ovaries removed at oophorectomy. The majority of these ovaries were not from the same pool as those studied in the theca cell experiments, since the method for theca cell culture was established later than that for granulosa cell culture. Pelvic congestion cystic ovaries were identified in seven pairs of ovaries, and in all patients but one pelvic congestion was the primary indication for surgery. Of the remaining pairs of ovaries, seven had polycystic and eight had normal ovarian morphology. Clinical details for the women with pelvic congestion cystic ovaries are shown in Table IIIGo. The mean (range) diameter of follicles from ovaries of each morphology was 9 (4–17) mm for pelvic congestion cystic, 4 (1–9) mm for normal, and 10 (9–16) mm for the polycystic ovaries. All the polycystic ovaries were from anovulatory subjects. Oestradiol production in the absence of testosterone was low, but detectable, in each experiment. However, there was a significant increase in oestradiol production in response to FSH by cells pooled from each pair of ovaries, as shown in Figure 2Go. In the normal ovary group, the granulosa cell FSH dose–response showed an increase in oestradiol production to a maximum effective dose of 2.5 ng/ml, beyond which production then fell. Granulosa cells from anovulatory polycystic ovaries were hyperresponsive to FSH, and produced six to 10 times more oestradiol compared with the normal group across the range of FSH doses tested. Despite this, the ED50 values were not different. Granulosa cells from pelvic congestion cystic ovaries by contrast showed a reduced response to FSH, and had not reached a peak of response at the maximum FSH dose used.


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Table III. Granulosa cell studies. Clinical spectrum of the six women with pelvic congestion cystic ovaries
 


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Figure 2. Oestradiol response to testosterone alone (left-hand panel) or testosterone with increasing doses of FSH in granulosa cells from eight normal ovaries ({square}), seven polycystic ovaries (PCO) (•), and eight pelvic congestion cystic ovaries ({blacktriangleup}). Cells were pooled from follicles of <=11 mm diameter from each patient to allow for valid comparisons between groups. Data show geometric means and errors. Using analysis of variance there was a significant effect of morphology on oestradiol production when normal and pelvic congestion ovaries were compared (P < 0.01).

 
Follicular fluid steroids
The analysis of follicular fluids aspirated from both normal and polycystic ovaries has been reported previously. In this study, 74 samples of follicular fluid collected from the ovaries of nine women with pelvic congestion cystic ovaries were analysed. Results are shown in Table IVGo. It is generally accepted from earlier studies (McNatty et al., 1981) that, for a follicle to be healthy, the follicular fluid must have an androgen:oestrogen ratio <4. In the present series, only five follicles fitted into this category; four of these had a diameter of >=15 mm and were clearly the pre-ovulatory or dominant follicles in each case. One had a diameter of 8 mm in a woman who also had a healthy 15 mm follicle. The prevalence of androgen-dominant follicles in this series of pelvic congestion ovaries suggests that these follicles are likely to be atretic cysts.


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Table IV. Median (range) follicular fluid oestradiol and androstenedione concentrations in follicles dissected from nine pairs of pelvic congestion cystic ovaries. The majority of these follicles were androgen-dominant, and could therefore be considered atretic
 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
In this study, a significant difference has been demonstrated in ovarian steroidogenesis by pelvic congestion cystic ovaries compared with both normal and polycystic ovaries. More importantly, pelvic congestion ovaries are clearly distinct from classical polycystic ovaries in both morphological and functional terms.

The results of this study are best interpreted in the light of the 2-cell, 2-gonadotrophin theory of folliculogenesis (Armstrong and Dorrington, 1979Go). During follicular growth, theca and granulosa cells work in synchrony to produce oestradiol. Under the influence of LH, the theca layer converts cholesterol to pregnenolone, which is then converted to androstenedione, the precursor for oestradiol formation. The key enzyme involved in androgen biosynthesis, 17{alpha}-hydroxylase cytochrome P450, is found almost exclusively in the theca layer. Aromatase, the enzyme converting androstenedione to oestradiol, is found predominantly in the granulosa layer, although a small amount is present in theca cells (Inkster and Brodie, 1991Go; Gilling-Smith et al., 1994Go). The majority of the androstenedione diffuses across the lamina basalis to the granulosa layer, where FSH stimulates its aromatization to oestradiol. The relative concentration of androstenedione and oestradiol in follicular fluid reflects the relative steroidogenic activities of the two cell layers. In this study, theca from pelvic congestion cystic and polycystic ovaries both demonstrated increased basal and LH-stimulated androstenedione production compared with the response from normal ovaries. In the pelvic congestion cystic ovary, enhanced theca androgen production almost certainly represents theca cell hyperplasia, which occurs during the process of follicular atresia (Hughesdon, 1982Go). This is consistent with finding that the majority of follicles in these ovaries were atretic, as evidenced by the high androgen:oestrogen ratio in the follicular fluid (McNatty, 1981Go) and the fact that the oestradiol response to FSH by granulosa cells was poor. By contrast, hyperplasia associated with atresia cannot account for increased theca cell steroidogenesis by polycystic ovaries since the proportion of atretic follicles in these ovaries, as judged by follicular fluid oestradiol content, is no higher than that in normal ovaries (Mason et al., 1994Go). Furthermore, granulosa cell responsiveness to FSH is similar to that in normal ovaries in the case of ovulatory subjects, or greater than that of normal ovaries in anovulatory subjects.

Increased theca cell androgen production in the polycystic ovary is thought to reflect an intrinsic abnormality of ovarian androgen biosynthesis rather than a response to atresia, particularly as progesterone production is also enhanced (Gilling-Smith et al., 1994Go). This concept is backed by in-vivo studies of ovarian androgen secretion (Gilling-Smith et al., 1997Go) and recent association and linkage studies which suggest the gene encoding cholesterol side chain cleavage may play a pivotal role in the aetiology of the condition (Franks et al., 1997Go; Gharani et al., 1997Go).

It was found that the prevalence of pelvic congestion cystic ovaries in our unpublished series of 61 ovaries removed from women with pelvic congestion was 23%, and the prevalence of polycystic ovaries was 21%. The latter is a similar value to that expected in the normal female population (Polson et al., 1988Go). In terms of abnormal ovarian steroidogenesis, as characterized in this report, just under one-half of the women with pelvic congestion have increased theca cell androgen biosynthesis. One hypothesis leading from these data is that increased local production of androgens, either alone or in combination with physiological concentrations of oestrogen, has a direct effect on the pelvic vasculature. Both testosterone and oestrogen have been found to produce a significant enlargement of ovarian and uterine veins in ovariectomized mice (Forbes and Kapadia, 1976Go). However, data linking androgens and venous dilatation in humans are tenuous.

Oestradiol production by theca cells is very low under normal circumstances. Although quite substantial amounts were being produced by theca from two of the pelvic congestion cystic ovaries, overall, there were no significant differences in theca cell oestradiol production between the three groups. The amount of oestradiol secreted by theca is unlikely to represent a significant contribution to the circulating pool of oestrogen.

The majority of women with pelvic congestion cystic ovaries in this series had regular—and presumably therefore ovulatory—cycles. Since it is not known whether these ovaries are associated exclusively with venous congestion, it is difficult to speculate on how these atretic cysts arise. One possibility is abnormal gonadotrophin stimulation. Preliminary studies on gonadotrophin pulsatility in women with venous congestion have shown abnormalities of LH pulsatility only in women with classic polycystic ovary syndrome (unpublished data). An alternative explanation is that ovarian factors generated during episodes of pain such as nerve growth factor, vasoactive intestinal peptide and noradrenaline result in disordered follicular growth (Ojeda et al., 1989Go).

It is accepted that the populations of ovaries studied in the theca and granulosa experiments were different, since the methodology for culturing theca cell cultures was established at a later date than that for granulosa cells. However, the conclusions drawn from this study are justified since they are based on within-group comparisons of theca and granulosa cell function in the three different types of ovaries. A further point is that one of the most important variables controlling steroidogenic output from either cell type is follicle diameter, and all follicles studied were <=10 mm in diameter.

The characterization of the pelvic congestion ovary as a distinct entity, morphologically and functionally, as described in this report, paves the way for further studies. The morphological definition is purely descriptive, and precise histological and ultrasound morphological criteria are needed if these findings are to have a practical clinical application. A preliminary histological analysis of dissected ovaries removed at oophorectomy was performed in which 41 full-width histology sections were analysed from 29 ovaries designated as pelvic congestion cystic by the descriptive criteria used in this report. Morphometric analysis revealed that each section contained an average of five cysts with a mean diameter of 8 mm (range 4–10.8 mm). It was observed that, unlike classic polycystic ovaries, the cysts in these ovaries tended to be arranged in clusters of three to five, often centrally distributed in a stroma which appeared loose and often oedematous. When compared with 23 previously stored histology sections of anovulatory polycystic ovaries, the cyst diameter and the percentage section occupied by the cysts were significantly greater in pelvic congestion cystic ovaries. A prospective histological analysis with larger numbers is clearly needed to establish strict morphological criteria for defining the pelvic congestion cystic ovary, and this should be performed in conjunction with both two- and three-dimensional pelvic ultrasound analysis of these ovaries before oophorectomy to enable ultrasound criteria to be likewise defined. With these criteria established, future studies should address the prevalence of pelvic congestion ovaries in asymptomatic women as well as in those with pelvic congestion to evaluate the full clinical significance of these ovaries.

Pelvic congestion ovaries are clearly distinguishable from classic polycystic ovaries on two-dimensional ultrasound (Adams et al., 1990Go). Figure 3Go shows the ultrasonographic features of normal, multicystic, polycystic and pelvic congestion ovaries, and illustrates the difficulties that ultrasonographers face when reporting ovarian morphology. Confusion between pelvic congestion ovaries and multicystic ovaries is inevitable unless close attention is paid to additional features present on the scan, such as uterine size and endometrial thickness. Women with multicystic ovaries have low oestrogen status, and consequently a small uterus and thin endometrium. By contrast, women with pelvic congestion have normal oestrogen concentrations, and the uterus and endometrium are either of normal or increased size (Adams et al., 1990Go). Clinically, multicystic ovaries are associated with oligomenorrhoea or amenorrhoea, while pelvic congestion ovaries are not usually associated with cycle disturbance.



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Figure 3. Ultrasonographic features of normal, polycystic, multicystic and pelvic congestion ovaries. Classic polycystic ovaries have a peripheral distribution of small follicles, typically 2–8 mm in diameter, increased density and amount of ovarian stroma and an increased ovarian volume (>9 ml). A dominant follicle is seen in ovulatory subjects. Multicystic ovaries, characteristic of hypothalamic amenorrhoea, have a normal or reduced ovarian volume and small follicles 4–10 mm scattered throughout a normal stroma (Adams et al., 1985Go). Pelvic congestion cystic ovaries have larger follicles, 7–11 mm in diameter, distributed in clusters throughout the ovarian stroma. The ovary is of normal volume with no increase in stromal density.

 
In conclusion, the existence of pelvic congestion cystic ovaries as a distinct entity, both morphologically and functionally is reported here for the first time. These ovaries have been previously identified on ultrasound in about one-quarter of women with pelvic congestion. In vitro, both theca and granulosa cells behave differently to those isolated from normal and polycystic ovaries and reflect the high proportion of atretic follicles in these ovaries. The factors leading to the generation of atretic follicles, and the significance of these ovaries in the aetiology of venous congestion, remain unknown.


    Notes
 
1 To whom correspondence should be addressed at: Assisted Conception Unit, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK. E-mail: cgs{at}chelwest.nhs.uk Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 
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Submitted on July 13, 2000; accepted on September 15, 2000.





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