Long term follow-up of patients with polycystic ovarian syndrome after laparoscopic ovarian drilling: clinical outcome

S.A.K. Amer,1, V. Gopalan, T.C. Li, W.L. Ledger and I.D. Cooke

Department of Obstetrics and Gynaecology, University of Sheffield, Jessop Wing, Sheffield Teaching Hospitals, Tree Root Walk, Sheffield S10 2SF, UK


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
BACKGROUND: Currently, there is an uncertainty about the impact of laparoscopic ovarian drilling (LOD) on the natural history of polycystic ovarian syndrome (PCOS). This longitudinal follow-up study was undertaken to investigate the long-term effects of LOD. METHODS: The study included 116 anovulatory PCOS women who underwent LOD between 1991 and 1999 (study group) and 34 anovulatory PCOS women diagnosed during the same period but who had not undergone LOD (comparison group). The hospital records were reviewed and questionnaires were sent to all the women. In addition, most women attended a follow-up interview. Clinical data recorded at different intervals of follow-up (short-term, <1 year; medium-term, 1–3 years; and long-term, 4–9 years) included: the menstrual pattern, symptoms relating to hyperandrogenaemia and reproductive history. RESULTS: The proportion of women with regular menstrual cycles increased significantly [relative risk (RR) = 1.6, 95% confidence interval (CI) = 1.4–1.9, P < 0.05] from 8% before LOD to 67% post-operatively. The proportion dropped to 37% (RR = 2.6, 95% CI = 1.8–3.8, P < 0.01) at medium-term follow-up and then increased again to 55% (RR = 2.2, 95% CI = 1.7–2.8, P < 0.01) at long-term follow-up. After LOD, 54/110 women (49%) conceived spontaneously during the first year and 42 (38%) during medium- and long-term follow-up. Among women with hirsutism (n = 43) and acne (n = 25), 10 (23%) and 10 (40%) respectively experienced long-term improvement after LOD. CONCLUSION: LOD produces long-term improvement in menstrual regularity and reproductive performance in about one-third of cases. A modest and sustained improvement in acne and hirsutism can be expected in ~40 and ~25% of patients respectively.

Key words: clinical outcome/laparoscopic ovarian drilling/long-term follow-up/menstrual pattern/polycystic ovarian syndrome


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
It has now been recognized that laparoscopic ovarian drilling/diathermy (LOD) is an effective second-line treatment for anovulatory infertility associated with polycystic ovarian syndrome (PCOS) (Li et al., 1998Go). However, there is still much controversy concerning the long-term impact of LOD on its natural history. Some investigators reported that the beneficial effect of LOD is rather transient (Gjonnaess, 1984Go; Keckstein et al., 1990Go; Armar and Lachelin, 1993Go), whereas others appear to indicate that the treatment may have long-term beneficial effects (Naether et al., 1994Go; Gjonnaess, 1998Go).

A previous study reported on the results of a long term-follow-up of 200 patients with PCOS after laparoscopic ovarian electrocautery (Naether et al., 1994Go). They followed patients for 6 years and noted that 145 patients achieved a total of 211 conceptions, giving a pregnancy rate of 70%. Moreover, they also presented data on menstrual cycle characteristics and androgen levels in these patients. However, in their study, they did not include a control population and it is therefore unclear as to what extent the observations could be attributed to the impact of laparoscopic ovarian electrocautery alone. This is particularly important, as a recent study suggested that some women with PCOS have spontaneous improvement in their menstrual characteristics and biochemistry with time, i.e. with increasing age, without any treatment (Elting et al., 2000Go). The same criticism also applies to another study (Gjonnaess, 1998Go) on the late endocrine effects of ovarian electrocautery in women with PCOS.

In this study, we report our observations from a longitudinal long-term study of women who underwent LOD for PCOS and compare our observations with a comparison group with the same condition but without the surgical intervention. We also examine factors that affect the results at long-term follow-up.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Subjects
Between 1991 and 1999, a total of 194 women with anovulatory infertility associated with PCOS underwent LOD in the Reproductive Medicine and Surgery Unit of the Jessop Hospital for Women. The hospital records of these 194 subjects were reviewed and a letter was sent to each patient to ask whether they were willing to participate in the follow-up study. Twenty-eight subjects were lost to follow-up, 20 declined to participate and 30 were unable to provide reliable follow-up data, because they had been on long-term hormone treatment including the combined oral contraceptive pill or had had hysterectomy (n = 8). The remaining 116 patients provided the data for our long-term follow-up study. All the women had anovulatory infertility of >1 year's duration, and had been unsuccessfully treated with clomiphene citrate (CC) of up to 150 mg/day for 5 days in the early follicular phase of the menstrual cycle prior to LOD. In 104 women, CC failed to induce ovulation (CC resistance). The remaining 12 patients ovulated but failed to conceive after CC treatment for 6–9 months. In addition, seven women had received HMG therapy for ovulation induction and failed to conceive. Most of the women (n = 96) attended a follow-up interview with one of the investigators (S.A.), during which time a blood sample was taken and a transvaginal scan was also carried out. The remaining 20 patients provided the clinical information on a structured questionnaire but did not attend the clinic for interview.

The South Sheffield Research Ethics Committee approved this study.

Comparison group
Thirty-four women with anovulatory infertility associated with PCOS were identified from the same hospital. They were diagnosed during the same period as the study population but had not undergone LOD. They constituted the comparison group. All the women had anovulatory infertility of >1 year's duration. Two subjects decided to postpone fertility treatment after their initial diagnosis and the remaining 32 women received CC. Twenty-eight attended for interview, blood tests and a transvaginal scan. The remaining six patients provided the clinical data on a structured questionnaire.

PCOS
In our study, the diagnosis of PCOS in both groups of women was based on the following criteria: (i) early follicular phase (defined as days 2–5 of the menstrual cycle) serum LH:FSH ratio was >=2 and/or raised serum androgen levels [testosterone >=2.5 nmol/l, androstenedione >=10 nmol/l or free androgen index (FAI) >4]. The FAI has been found to be a useful test for detecting patients with PCOS (Eden et al., 1989Go), and is calculated using the formula testosteronex100/sex hormone-binding globulin (SHBG) (Carter et al., 1983Go); in women who were oligo/amenorrhoeic, a random blood sample was accepted; or (ii) there was ultrasonographic evidence of ovarian stromal hypertrophy and multiple (>=10), small (6–8 mm) follicles arranged in the periphery (Adams et al., 1985Go).

Laparoscopic ovarian drilling
The techniques of LOD used in our centre have been previously published (Li et al., 1998Go). More than 10 gynaecologists of varying degrees of experience (Senior House Officers under supervision, Registrars and Consultants) carried out the treatment over the 9 year period. Two forms of energy sources were used, either argon laser (n = 14) or monopolar diathermy (n = 102). In most cases, a three-puncture laparoscopy was performed. A 10 mm laparoscope was inserted via the main subumbilical route and a pair of grasping forceps was introduced through one of the two lower abdominal 5 mm punctures to grasp the utero-ovarian ligament and to lift the ovary away from the bowel. The third entry was used to introduce the diathermy needle or the laser fibre.

In diathermy treatment, a specially designed probe (Rocket of London, Watford, UK) was used to penetrate the ovarian capsule at a number of points with the aid of a short burst of diathermy. The probe has a distal stainless steel needle measuring 8 mm in length and 2 mm in diameter projecting from an insulated solid cone of 6 mm maximum diameter. The electrosurgical unit used was the Force 2 Valleylab electrosurgical generator (Valleylab Inc., Boulder, Colorado, USA). A monopolar coagulating current at 30 W power setting was used and the duration of each penetration was ~5 s. Three to 10 punctures were made in each ovary depending on its size, each measuring 4 mm in diameter and 5–7 mm in depth. Each ovary was cooled by irrigation using Hartmann's solution before releasing the ligament.

Laser treatment was performed with an argon laser (HMG Inc., Medical Laser Systems, Salt Lake City, Utah, USA), with the power setting at 12–14 W in continuous mode. A disposable sapphire tip connected to a 600 mm flexible fibre (GynCath 600; HGM Inc., Medical Laser Systems, Salt Lake City, Utah, USA) delivered the laser energy in contact mode. Depending on the size of the ovary, between 10 and 40 holes were made in the ovarian capsule. Laser was applied for 1 s during the drilling of each hole.

Post-operative monitoring
Following ovarian drilling, women were asked to keep a record of their menstrual cycle. If the patient started a menstrual period within 6 weeks of the surgery, a blood sample was taken on day 2 of that cycle for measurement of serum concentrations of LH, FSH, testosterone, androstenedione and SHBG. Another blood sample was taken on day 21 of the same cycle for measurement of serum concentration of progesterone. Ovulation was diagnosed when the progesterone level was >=30 nmol/l. Two more mid-luteal phase blood samples were taken in the subsequent cycles to measure serum progesterone levels.

Follow-up data
The menstrual pattern, the presence or absence of acne and hirsutism and the detailed reproductive history including any pregnancy and its outcome prior to LOD were documented. The same information was recorded at different intervals following LOD; short-term, <1 year; medium-term, 1–3 years; and long-term, 4–9 years.

The age of the patient when the diagnosis of the condition was made, other demographic details including body mass index (BMI), primary or secondary infertility, and the duration of infertility were also documented. Any pregnancy following laparoscopic ovarian diathermy and the outcome were documented.

For statistical analysis, the data were entered into the Statistical Package for Social Sciences (SPSS) for PC version 10.0.5. The appropriate statistical tests including 2x2 contingency table analysis, relative risk (RR) and Student's t-test were used to compare the results.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
A total of 116 patients were included in this study. The characteristics of this group of subjects are shown in Table IGo. The characteristics of women in the comparison group are shown in the same table.


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Table I. The characteristics of 116 polycystic ovarian syndrome (PCOS) women who had laparoscopic ovarian drilling (LOD) for anovulatory infertility and 34 anovulatory PCOS women who had not undergone LOD
 
Menstrual pattern
In Figure 1Go, the proportion of women with normal menstrual cycles prior to LOD, and the results at short-, medium- and long-term follow-up are shown. The results are compared with the comparison group and show that the proportion of women who underwent LOD who had regular menstrual cycles at short-term follow-up (67%) [relative risk (RR) = 1.6, 95% CI = 1.4–1.9, P < 0.05], medium-term follow-up (37%) (RR = 2.6, 95% CI = 1.8–3.8, P < 0.01), and long-term follow-up (RR = 2.2, 95% CI = 1.7–2.8, P < 0.01) were all significantly greater than the proportion (8%) prior to LOD. By comparison, the pattern in the control subjects (Figure 1Go) showed a similar short-term significant increase in the proportion of women with regular menstrual cycles from 6% prior to the treatment to 56% while on CC; followed by a drop to pre-treatment frequency (12%) in the medium-term follow-up. At the long-term follow-up, the proportion increased significantly to 26%. However, the proportions of women with a normal menstrual cycle at the medium- and long-term follow-up after LOD were significantly (P < 0.05) greater than that of the control subjects during the corresponding periods of follow-up.



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Figure 1. The proportion of women with polycystic ovarian syndrome having regular menstrual cycles before treatment and during the three periods of follow-up. The grey bars represent women who underwent laparoscopic ovarian drilling (LOD), whereas the white bars represent women who did not (comparison group). Two-by-two contingency table analysis was used to compare the two groups before treatment and during the three periods of follow-up: before treatment, not significant; short-term, not significant; medium-term, P < 0.01; long-term, P < 0.01. *Four women conceived after LOD before any period. **Two women did not receive clomiphene citrate.

 
In Figure 2Go, the relationship between the duration of follow-up in years after LOD and the proportion of women with regular menstrual cycles was examined in greater detail. It showed a biphasic pattern: the proportion of women with a regular cycle significantly increased in the first year after LOD, then dropped significantly at years 2 and 3, but returned to a level similar to that seen at year 1 after LOD by years 5 and 6.



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Figure 2. The proportion of women with regular menstrual cycles before and at yearly intervals following laparoscopic ovarian drilling (LOD). 0: before LOD (n = 116); Y1: 1st year after LOD (n = 112); Y2: year 2 after LOD (n = 116); Y3: year 3 after LOD (n = 89); Y4: year 4 after LOD (n = 68); Y5: year 5 after LOD (n = 62); Y6: year 6 after LOD (n = 54); Y7–9: years 7–9 after LOD (n = 44).

 
Acne and hirsutism
Among the 116 women who had LOD, 43 (37%) experienced hirsutism and 25 (22%) acne. The impact of LOD on these two symptoms is summarized in Table IIGo. Among the 34 control subjects, 17 experienced hirsutism, and seven acne. As the number in the control groups who experienced these two symptoms is small, it is not possible to make direct comparison between the two groups. Nevertheless, there appears to be a trend towards a modest improvement in these two symptoms (hirsutism 33%, acne 52%) amongst those who reported these symptoms prior to LOD. The improvement in hirsutism and acne was sustained during the medium- and long-term follow-up periods in 23 and 40% respectively.


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Table II. The impact of laparoscopic ovarian drilling on hirsutism and acne in women with polycystic ovarian syndrome
 
Conception
Reproductive performance before LOD
Among the 116 women who underwent LOD, 48 had conceived at least once prior to the treatment producing 87 pregnancies; of these, 47 (54%) resulted in spontaneous miscarriage. Seven women (6%) had three or more miscarriages. The details are summarized in Table IIIGo.


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Table III. Reproductive history in 116 women with polycystic ovarian syndrome prior to laparoscopic ovarian drilling
 
Reproductive performance after LOD
The number of spontaneous conceptions occurring in each of the three follow-up periods after LOD is summarized in Table IVGo. Six women opted to delay conception due to change in social circumstances after LOD. Among the remaining 110 women, 54 (49%) conceived during the first year. Forty-two (38%) women conceived during medium- and long-term follow-up: 13 (12%) for the first time and 29 (26%) achieved further pregnancies. In total, 67/110 women (61%) conceived spontaneously during the periods of follow-up after LOD. Amongst these 67 women, 34 (51%) conceived again later at least once, producing 53 subsequent spontaneous conceptions, resulting in a total of 120 spontaneous conceptions. Of these pregnancies, 20 (17%) resulted in miscarriages, whereas four (3%) were tubal pregnancies. Among the 110 women, 62 (56%) had at least one spontaneously conceived livebirth after LOD; 47 (43%) during the first 12 months, 10 during medium-term and five during long-term follow-up.


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Table IV. The outcome of spontaneous conceptions of the 116 women with polycystic ovarian syndrome after laparoscopic ovarian drilling (LOD) during the three periods of follow-up

 
Reproductive performance of the comparison group
The data for the comparison group are summarized in Table VGo. Two women opted to delay their fertility treatment after their initial diagnosis. Of the remaining 32 women, 18 (56%) conceived at least once, producing 27 pregnancies during the periods of follow-up. Of the 27 pregnancies, six (22%) ended in miscarriages. There was no incidence of ectopic pregnancy in this group. Fourteen (44%) women had at least one livebirth during the periods of follow-up. There were no assisted conceptions in the comparison group.


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Table V. The outcome of conceptions among 34 women with polycystic ovarian syndrome who had not undergone laparoscopic ovarian drilling (comparison group)

 
Pregnancies resulting from assisted conception were analysed separately for women who underwent laparoscopic ovarian diathermy (Table VIGo).


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Table VI. The outcome of pregnancies arising from assisted conception following laparoscopic ovarian drilling

 
Factors affecting outcome
The possible impact of age and BMI on the results of the follow-up was analysed. Age at the time of follow-up had a significant impact on the menstrual pattern after LOD. In women who were aged >=36 years, the proportion with regular cycles (65%), was significantly (P < 0.01) higher than that (39%) of women aged <=35 years (Figure 3Go). In contrast, the BMI at the time of follow-up did not appear to have any impact on the menstrual cycle pattern. In women who had a BMI of >25 kg/m2, the proportion with a regular cycle was 39%, which was not significantly different (P = 0.08) from that of women with BMI of <=25 kg/m2 (54%).



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Figure 3. An analysis of the impact of age on the menstrual pattern during the long-term follow-up of polycystic ovarian syndrome women who underwent laparoscopic ovarian drilling: two-by-two contingency table analysis between the two groups, P < 0.01.

 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
In this paper, we have described our observations of a long-term follow-up study of 116 women who underwent LOD for PCOS and compared the results with a group of subjects with the same condition, but who had not undergone LOD.

Menstrual cycle pattern
Eight per cent of women in the study group had regular menstrual cycles prior to LOD. Although chronic anovulation in women with PCOS is usually associated with menstrual irregularities (Franks, 1995Go), several authors have reported that a proportion of these women do have apparently `regular' menstrual cycles. One study reported that 21% of anovulatory PCOS women have regular menstrual cycles (Carmina and Lobo, 1999Go); another reported a 24% incidence of regular menstrual cycles amongst anovulatory PCOS patients undergoing ovarian diathermy (Naether et al., 1994Go). A review of 187 reports describing 1079 cases of PCOS reported a 16% incidence of regular menses (Goldzieher and Axelrod, 1963Go). This observation was confirmed in a recent study of 1741 women with PCOS in which 30% of patients had regular menses (Balen et al., 1995Go).

We observed that the proportion of women with regular menstrual cycles increased significantly from 8% prior to LOD to 67% after surgery. However, the proportion dropped in year 2 (medium-term follow-up) to 37% and reverted back to 62% by year 5. Many authors observed that LOD restored menstrual regularity in a significant proportion (63–86%) of women (Gjonnaess, 1984Go; Naether et al., 1993Go; Li et al., 1998Go; Felemban et al., 2000Go). Naether et al. reported that among the menstrual cycles examined after LOD the proportion of regular cycles was ~80% at 1–3 months, 82% at 6–24 months and 92% at 36–72 months post-operatively (Naether et al., 1994Go). In our study, while the results of the short-term follow-up are comparable to those of Naether et al., the medium-term follow-up data showed that the proportion of women with regular menstrual cycles had dropped to 37% (Naether et al., 1994Go). One would therefore speculate that the beneficial effect of laparoscopic ovarian surgery had worn off after 1 year in ~45% of women who initially responded to the treatment. Interestingly, the long-term follow-up data suggest that a significantly higher proportion of women (55%) had a regular menstrual cycle compared with that observed at medium-term follow-up. The latter increase may be a phenomenon related to the natural history of PCOS, in that as women become older, the underlying endocrine abnormality become less pronounced and therefore their cycles become relatively more regular (Dahlgren et al., 1992Go; Elting et al., 2000Go). This is further supported by the observation that in the control group there is also a steady trend towards an increasing proportion of women having a normal menstrual cycle at long-term follow-up compared with those of the medium-term follow-up. Our hypothesis is further strengthened by the analysis in Figure 3Go, which shows that older women (>35 years) are more likely to have regular cycles at the time of the follow-up compared with women who were <=35 years. However, it appears that LOD has a long-term beneficial impact on the menstrual cycle regularity since the proportions of women with normal menstrual cycles at medium- and long-term follow-up after surgery were significantly greater than that of the women who had not undergone LOD (comparison group) during the corresponding follow-up periods.

Acne and hirsutism
In our population, LOD produced short-term improvement in hirsutism and acne in 33 and 52% of cases respectively and the effect seems to be sustained for up to 9 years in 23 and 40% of cases respectively. Our observations are consistent with the observation of a modest improvement in symptoms relating to hyperandrogenaemia (Naether et al., 1994Go). As the number of women assessed for hyperandrogenaemia in the comparison group is only small, formal statistical analysis/comparison is not possible. Nevertheless, the modest improvement in symptoms relating to hyperandrogenaemia is consistent with earlier observations that the FAI and plasma testosterone dropped in response to LOD (Gjonnaess and Norman, 1987Go; Armar et al., 1990Go; Kovacs et al., 1991Go; Naether et al., 1994Go). At present, LOD should not be considered as standard treatment for women with symptoms due to hyperandrogenaemia, as there are effective medical treatments available including the use of anti-androgens. There has never been any formal study to assess to what extent LOD improves the symptoms of acne and hirsutism.

Conception
Overall, 67 of 110 women (61%) conceived spontaneously following LOD; of these, 34 (31% of the total number of women) conceived again later at least once, producing 53 subsequent spontaneous conceptions, resulting in a total of 120 conceptions. One can therefore conclude that the beneficial impact of LOD on the reproductive performance appears to last for several years in >=31% of patients. This percentage represents a minimum number because a proportion of women who conceived once only have chosen not to conceive again after the first pregnancy.

Amongst the 110 patients, 13 (12%) conceived spontaneously for the first time >1 year after LOD. However, it is unreasonable to ask women to wait for several years after a specific treatment for spontaneous conception to occur. Patients want to know at the end of a reasonable period, e.g. a year, what the chances of spontaneous conception would be. In our series, the spontaneous conception rate at the end of 12 months is 49%, consistent with our earlier reports (Li et al., 1998Go).

The impact of LOD on the miscarriage rate
It is still debatable whether or not the miscarriage rate in women with PCOS is increased compared with the average population. Earlier studies suggest an increase in miscarriage rate (30–40%) in PCOS (Garcia et al., 1977Go; Homburg et al., 1988Go; Sagle et al., 1988Go). Regan et al. found that women with high serum LH concentrations had a miscarriage rate of 65% (Regan et al., 1990Go). In a prospective randomized controlled trial (Abdel-Gadir et al., 1990Go), the miscarriage rate following LOD was ~21%, which appeared to be significantly lower than that following ovulation induction by HMG or FSH (53 and 40% respectively).

In our study, we observed that there is a difference in the miscarriage rate between the study group prior to LOD (54%) and the comparison group (22%). This is not surprising as both groups are selected sub-populations of the PCOS patients: women who produce a successful pregnancy either spontaneously or with the help of CC will not therefore require LOD and are more likely to be placed in the comparison group, whereas women who fail to achieve a successful pregnancy either spontaneously or with the help of CC are more likely to proceed to LOD and hence enter the study group. It appears that the miscarriage rate in the comparison group was 22%, which is not far from that expected from the average population, whereas the miscarriage rate in the study group prior to treatment was 54%, which is significantly higher than that of the general population. Interestingly, the miscarriage rate in the latter subpopulation was significantly reduced to 17% (P < 0.001) after LOD. Our observation is consistent with a recent report (Abdel-Gadir et al., 1990Go) and suggests that LOD reduces the miscarriage rate in women with PCOS who are CC resistant. However, one cannot say that LOD should replace CC treatment on the ground that it has an additional benefit of reducing the miscarriage rate, because our data suggest that a subgroup of patients, such as the comparison group in our study, did not experience an excessively high miscarriage rate. However, there is a strong case for offering LOD to women with PCOS who also experience a history of recurrent pregnancy loss.

PCOS and recurrent miscarriage
In our study, we observed a 6% incidence of recurrent miscarriage (>=3 miscarriages) in the study group prior to LOD, which is significantly higher than that expected in the general population (~1%). The relationship between PCOS and recurrent miscarriage remains uncertain: whereas previous reports suggested that PCOS is a significant cause of recurrent miscarriage (Sagle et al., 1988Go; Regan et al., 1990Go; Tulppala et al., 1993Go; Clifford et al., 1994Go; Rai et al., 1996Go), more recent reports have questioned the importance of PCOS as a common cause of recurrent miscarriage (Li et al., 2000Go) and its prognostic relevance in women with recurrent pregnancy loss (Rai et al., 2000Go). Whereas most previous studies on the relationship between PCOS and recurrent miscarriage focused on a group of women with recurrent pregnancy loss, there is very little literature information on the outcome of pregnancies in women with PCOS. Taking the current literature data into consideration, it appears that there is a definite association between the two conditions: ~6% of women with PCOS experience recurrent miscarriage and ~8% of women with recurrent miscarriage have PCOS (Li et al., 2000Go). What we have shown in this study is that women with PCOS who failed to produce successful pregnancies with the help of CC have a higher prevalence of recurrent pregnancy loss than the average population. It is inappropriate to extrapolate our observation to all cases of PCOS, especially to those who respond successfully to CC and produce pregnancies. Interestingly, the number of women who experienced recurrent miscarriage dropped from seven (6%) prior to surgery to one (< 1%) post-operatively. In our study, we did not observe any case of recurrent pregnancy loss among the control subjects. However, the number in the control group is too small to permit a firm conclusion to be drawn. Nevertheless, based on previous literature data that ~40% of women with PCOS will successfully conceive with CC, one can therefore estimate that the prevalence of recurrent miscarriage among all cases of PCOS is >=3.6%, which is still higher than that of the average population (assuming that none of the women in the control group had recurrent miscarriage).

The overall conclusion is therefore that there is a definite association between the two conditions, but the association is not particularly a strong one: only a small proportion of women with recurrent miscarriage are expected to have PCOS (8%), and up to 6% of women with PCOS will experience recurrent pregnancy loss.

Factors affecting the outcome
Increasing age at long-term follow-up was associated with an increase in the incidence of regular menstrual cycles. As discussed above, this could be explained by the natural history of PCOS, in that patients tend to gain regular cycles, as they get older (Elting et al., 2000Go). On the other hand, BMI did not appear to influence the menstrual cycle pattern at the time of follow-up.

In conclusion, about two-thirds of women undergoing LOD respond to the treatment as evidenced by the resumption of regular menstrual cycles. In about half of the responders (i.e. a third of the total number of women), the effects seem to be permanent. As far as conception is concerned, women could expect ~1:2 chance of spontaneous conception within the first year with a reduction in the incidence of miscarriage (~17%). The improvement in the reproductive performance seems to last for many years in about a third of cases. A modest and sustained improvement in acne and hirsutism can be expected in about 40 and 25% respectively.


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
We are grateful for all the women who participated in the study and to Tricia Graham for typing the manuscript. We are also grateful for the valuable help of Elizabeth Tuckerman, Barbara Anstie and Dr Susan Laird of the Biomedical Research Unit of the Royal Hallamshire Hospital.


    Notes
 
1 To whom correspondence should be addressed. E-mail: s.amer{at}sheffield.ac.uk Back


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
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Submitted on January 2, 2002; accepted on April 18, 2002.