Long-term follow-up of patients with polycystic ovary syndrome after laparoscopic ovarian drilling: endocrine and ultrasonographic outcomes.
ABSTRACT There is considerable controversy as to how long the beneficial effects of laparoscopic ovarian drilling (LOD) last. 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.
- SourceAvailable from: sciencedirect.com[Show abstract] [Hide abstract]
ABSTRACT: To evaluate the effects of laparoscopic ovarian drilling (LOD) on three-dimensional (3D) power Doppler indices of ovarian stromal blood flow and serum vascular endothelial growth factor (VEGF) levels in women with polycystic ovary syndrome (PCOS).Middle East Fertility Society Journal 10/2014;
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ABSTRACT: The treatment of infertile women with polycystic ovary syndrome (PCOS) has not yet been established. Before any intervention is initiated, lifestyle modification with diet and exercise leading to weight loss should be emphasized in overweight women. The recommended first-line treatment for ovulation induction remains clomiphene citrate. If clomiphene citrate use fails to result in ovulation or pregnancy, the recommended second-line intervention is exogenous gonadotropins. The use of exogenous gonadotropins is related to an increased risk for multiple pregnancies, and, therefore, intense ovarian response monitoring is required. Laparoscopic ovarian surgery is an alternative to gonadotropin therapy because this surgery is as effective as gonadotropin in pregnancy rate or live birth rate. However, the surgery may require additional ovulation induction drug and should be performed by well-trained surgeon, its use solely to induce ovulation is unwarranted. Recommended third-line treatment is in vitro fertilization (IVF). IVF reduces the risk of multiple pregnancies by using single-embryo transfer in women with PCOS. The use of metformin alone as first-line infertility therapy or in combination with clomiphene is surrounded by controversies. Aromatase inhibitors appear to be as effective as clomiphene citrate for induction of ovulation, but the drug is currently not approved for treatment of infertility. Further studies should demonstrate the efficacy and long term safety.Korean Journal of Obstetrics and Gynecology. 01/2010; 53(10).
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ABSTRACT: In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30–100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P,0.05) and reduced antral follicle numbers after 5 weeks (P,0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P,0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P,0.05) and an increased ovarian resistance index (P,0.05) both of which persisted at 5 weeks (P,0.01; P,0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles. Citation: Connolly F, Rae MT, Butler M, Klibanov AL, Sboros V, et al. (2014) The Local Effects of Ovarian Diathermy in an Ovine Model of Polycystic Ovary Syndrome. PLoS ONE 9(10): e111280. doi:10.1371/journal.pone.0111280 Copyright: ß 2014 Connolly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper. Funding: This research was funded by the Medical Research Council (G0901807) and WCD was supported by a Senior Clinical Fellowship from the Scottish Funding Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.PLoS ONE 10/2014; 9(10):e111280. · 3.53 Impact Factor
Human Reproduction Vol.17, No.11 pp. 2851–2857, 2002
Long-term follow-up of patients with polycystic ovary
syndrome after laparoscopic ovarian drilling: endocrine
and ultrasonographic outcomes
S.A.K.S.Amer1, Z.Banu, T.C.Li and I.D.Cooke
Jessop Wing, Sheffield Teaching Hospitals, University of Sheffield, Tree Root Walk, Sheffield S10 2SF, UK
1To whom correspondence should be addressed. E-mail: email@example.com
BACKGROUND: There is considerable controversy as to how long the beneficial effects of laparoscopic ovarian
drilling (LOD) last. This follow-up study was undertaken to investigate the long-term effects of LOD. METHODS:
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. RESULTS: 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.
CONCLUSION: The beneficial endocrinological and morphological effects of LOD appear to be sustained for up
to 9 years in most patients with PCOS.
Key words: endocrine effects/laparoscopic ovarian drilling/long-term follow-up/polycystic ovary syndrome/polycystic ovaries
Laparoscopic ovarian drilling (LOD) has now been accepted
as a second-line treatment for anovulatory infertility due to
polycystic ovary syndrome (PCOS) after failure of a course
of clomiphene citrate (CC) (Li et al., 1998). Not only does
LOD produce high ovulation and pregnancy rates (Gjonnaess,
1998; Armar et al., 1990), but it also corrects the endocrine
abnormalities associated with the syndrome. The immediate
endocrine responses to LOD are similar to those previously
described after wedge resection indicating that the effects are
similar (Armar et al., 1990). After LOD, the main hormonal
changes reported in many studies include a rapid and persistent
fall of androgens (testosterone and androstenedione) with a
transient increase of gonadotrophins (LH and FSH) during the
first 24–48 h, followed later by a gradual fall (Aakvaag and
Gjonnaess, 1985; Gjonnaess and Norman, 1987; Greenblatt
and Casper, 1987). Although the short-term endocrine effects
of LOD have been extensively investigated, it is still uncertain
as to how long these effects last. Some investigators have
reported that the endocrine effects of LOD are rather transient
(Keckstein et al., 1990; Armar and Lachelin, 1993), whereas
others have indicated that the treatment might have long-term
beneficial effects (Gjonnaess, 1994; Naether et al., 1994).
© European Society of Human Reproduction and Embryology
In a long-term follow-up study, Gjonnaess reported on the
late endocrine effects of LOD in 51 women (Gjonnaess, 1998).
He concluded that ovarian electrocautery in women with PCOS
normalizes the serum levels of androgens and LH and that the
results appear to be sustained for 18–20 years. However, this
study did not include a control population and it is therefore
unclear to what extent the long-term observations could be
attributed to the impact of LOD alone. This is particularly
important as a study by Elting et al. suggested that some
women with PCOS do have spontaneous improvement in their
menstrual characteristics with increasing age, without any
treatment (Elting et al., 2000). The same criticism also applies
to the study by Naether et al., who reported on the long-
term effect of LOD on serum androgen (testosterone and
dehydroepiandrosterone) levels in 206 patients (Naether et al.,
1994). In a previous study, we reported on the clinical outcome
at medium- and long-term follow-up of the same group of
patients (Amer et al., 2002). In this study, we wish to report
our observations of the medium- and long-term endocrine and
ovarian changes in women who underwent LOD for PCOS
and compare our observations with a group of women with the
same condition but without surgical intervention (comparison
group). We also wish to examine factors that affect the results
at long-term follow-up.
by guest on May 29, 2013
S.A.K.S.Amer et al.
Materials and methods
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. Afterwards, a
letter was sent to the patients to ask if 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
including the combined oral contraceptive pill, or had had hysterec-
tomy (n ? 8). The remaining 116 patients provided the data for our
study. All the women had anovulatory infertility of ?1 year duration
and had been unsuccessfully treated with CC at 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.), at which time a blood sample and a transvaginal
scan were carried out.
A total of 34 women with anovulatory infertility associated with
PCOS who were diagnosed during the same time period of the study
but had not undergone LOD were identified from the same hospital.
These women constituted the comparison group. All the women had
anovulatory infertility of ?1 year duration. Two subjects decided to
postpone fertility treatment after their initial diagnosis and the
remaining 32 women received CC. Twenty-eight of these subjects
attended for interview, blood tests and a transvaginal scan.
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 ?2 and/or raised serum
androgen concentrations [testosterone ?2.5 nmol/l, androstenedione
?10 nmol/l or free androgen index (FAI) ?4]. FAI was calculated
using the formula: testosterone ?100/sex hormone-binding globulin
(SHBG) (Carter et al., 1983; Eden et al., 1989). In women who were
oligo/amenorrhoeic, a random blood sample was acceptable. (ii)
There was ultrasonographic evidence of ovarian stromal hypertrophy
and multiple small (6–8 mm) follicles arranged in the periphery
(Adams et al., 1985).
The techniques of LOD used in our centre have previously been
published (Li et al., 1998; Amer et al., 2002).
Patients underwent transvaginal scanning prior to LOD (n ? 101)
and at medium- (1–3 years, n ? 36) and long-term (4–9 years, n ?
67) intervals after surgery. Two ultrasound machines of the same
model (Toshiba, model Sonolayer SSA-250A, with a convex 6-MHz
transvaginal ultrasound probe) have been used in our unit during the
9 year follow-up period. At medium- and long-term follow-up, women
with regular menstrual cycles were scanned on days 2–5 of the
cycle, whereas women with severe oligomenorrhoea were not timed
according to the menstrual cycle. Each ovary was localized in relation
to the iliac vessels, and scanned from inner to outer margins in
longitudinal cross-sections and from upper to lower ends in transverse
cross-sections. The three diameters of the ovary were measured
(longitudinal, anteroposterior and transverse). The ovarian volume
0.523?length?width?thickness, according to the method of Sample
et al. (Sample et al., 1977). The mean volume of the right and left
ovary was calculated for each subject.
ofa prolate ellipsoid:
Collection of blood samples
Blood samples were taken from women in both groups early in the
follicular phase (defined as days 2–5 of the menstrual cycle) or at a
random time in women with severe oligomenorrhoea or amenorrhoea.
The samples were collected from the patients prior to LOD and at
different intervals following surgery: short- (?1 year), medium-
(1–3 years) and long-term (4–9 years).
Serum hormonal concentrations were measured using well-established
assays, which have been validated in our laboratory at the Department
of Clinical Chemistry, Royal Hallamshire Hospital. These assays,
which have previously been described (Okon et al, 1998; Li et al,
2000), were not changed between 1991 and 2000, i.e. the same assays
were used at the different periods of follow-up.
The endocrinological and ultrasonographic data were documented
before and at different intervals (short-, medium- and long-term) after
LOD. The age of the patients, when the diagnosis of the condition
was made and other demographic details, including body mass index
(BMI), primary or secondary infertility and the duration of infertility,
were also documented.
For statistical analysis the data were entered into the Statistical
Package for Social Sciences (SPSS) for PC version 10.0.5. Continuous
data were compared by Mann–Whitney U-test and Wilcoxon signed
ranks test.Comparisons ofcategorical data werecarried out using2?2
contingency table analyses. Significance was assumed if P ? 0.05.
The South Sheffield Ethics Committee approved this study.
A total of 116 patients was included in this part of the study.
The demographic, clinical and endocrinological characteristics
of this group of subjects are shown in Table I. The character-
istics of the comparison subjects are also shown in the
The serum concentrations of LH and the LH:FSH ratio
decreased significantly after LOD and remained low during
the medium- and long-term follow-up (Figure 1). In compar-
ison, the serum LH concentrations and the LH:FSH ratio of
women in the comparison group did not show significant
changes during the same time periods.
Comparison of the proportion of women with high LH
concentrations (?10 IU/l) before and after LOD showed a
significant (P ? 0.01) decrease from 70% prior to LOD to
33% shortly after surgery. The proportion remained low during
the medium- and long-term follow-up periods (45 and 31%
by guest on May 29, 2013
Laparoscopic ovarian drilling for PCOS
Table I. The characteristics of 116 women with polycystic ovary syndrome (PCOS) who had laparoscopic
ovarian drilling (LOD) for anovulatory infertility and 34 anovulatory PCOS women who had not undergone
Mean ? SDRange
Mean ? SD Range
Age at follow-up (years)
Body mass index (kg/m2)
Duration of infertility (years)
Serum LH (IU/l)
Serum FSH (IU/l)
Serum LH:FSH ratio
Serum testosterone (nmol/l)
Serum androstenedione (IU/l)
Free androgen index
Ovarian volume (ml)
33.3 ? 4.4
26.7 ? 4.9
3.1 ? 2.1
14.4 ? 7.5
5.4 ? 1.5
2.7 ? 1.2
2.6 ? 1.3
9.8 ? 4.0
8.6 ? 8.2
11.0 ? 3.7
32.2 ? 4.9
29.9 ? 7.9
1.8 ? 1.8
13.0 ? 6.2
5.0 ? 1.6
2.6 ? 1.4
3.2 ? 1.2
11.0 ? 3.9
11.3 ? 7.3
11.5 ? 5.2
Menstrual cycle patterna
Other subfertility factors
Ultrasound evidence of PCO
Clomiphene ? hMG
aMenstrual patterns definition: regular cycles, cycle length between 25 and 35 days; oligomenorrhoea, cycle
length between 35 days and 6 months; amenorrhoea, absence of the menstrual period for ?6 months.
PCO ? polycystic ovaries.
respectively). In contrast, the proportion of women in the
comparison group with LH concentrations ?10 IU/l (67%)
did not show significant changes during the same follow-up
There was no significant change in the serum concentrations
of FSH after LOD in either group (Figure 1b). The mean
serum FSH concentrations remained ~5 IU/l throughout the
follow-up periods after LOD. At long-term follow-up, the FSH
levels ranged between 1.1 and 13.5 IU/l. Up to 9 years after
surgery, there was no case of premature ovarian failure (POF)
among women who underwent LOD.
In Figure 2, the serum concentrations of testosterone, andros-
tenedione and SHBG and the FAI before LOD and at the three
periods of follow-up are shown. The mean serum testosterone
concentration and FAI decreased significantly after LOD and
remained low throughout the follow-up periods. The mean
serum concentration of androstenedione showed no significant
change shortly after LOD, but showed a significant reduction
at medium- and long-term follow-up. The number of subjects
in the comparison group who had their androgen levels
measured at medium-term follow-up was too small for it to
be possible to make direct comparison between the two groups.
The serum testosterone concentrations and FAI of women who
had not undergone LOD did not show significant change at
long-term follow-up (Figure 2). However, the mean serum
androstenedione concentration of the comparison group
decreased significantly (P ? 0.05) at that time.
The percentage of women with FAI ?4 showed a significant
(P ? 0.01) decrease from 69% prior to LOD to 41% shortly
after surgery. The value remained low (33–35%) during the
by guest on May 29, 2013
S.A.K.S.Amer et al.
Figure 1. Serum LH and FSH concentrations and LH:FSH ratio in
women with PCOS before treatment and during the three periods of
follow-up. Data show mean values –1 SEM. The filled columns
represent women who underwent LOD, whereas the open columns
represent women who did not (comparison group). Mann–Whitney
test was used to compare the two groups. (a) LH: before treatment,
not significant; medium-term, not significant; long-term, P ? 0.01;
(b) Serum FSH concentrations: before treatment, not significant;
medium-term, not significant; long-term, not significant; (c) Serum
LH:FSH ratio: before treatment, not significant; medium-term, not
significant; long-term, P ? 0.01. Wilcoxon signed ranks test was
used to compare the values in women who underwent LOD at
the three periods of follow-up with the pre-operative values
(**P ? 0.01, ***P ? 0.001). Med.-term ? medium-term.
medium- and long-term follow-up periods. On the other hand,
the proportion of women in the comparison group with FAI
levels ?4 IU/l (81%) did not show significant changes at long-
term follow-up (70%).
of polycystic ovaries (PCO) prior to treatment and at medium-
and long-term follow-up, are shown. The results show that
the proportion of women with ultrasound evidence of PCO
significantly (P ? 0.01) decreased after LOD and remained
low during the follow-up periods. By contrast, no similar
changes were observed in the comparison group during the
corresponding follow-up periods. Figure 3b shows the mean
Figure 2. Serum androgen concentrations in women with PCOS
before treatment and during the three periods of follow-up. Data
show mean values and –1 SD. The filled columns represent women
who underwent LOD, whereas the open columns represent women
who did not (comparison group). Mann–Whitney test was used to
compare the two groups before treatment and at long-term follow-
up. Before treatment, not significant; long-term, P ? 0.01 to
? 0.001 [except sex hormone-binding globulin (SHBG), not
significant]. The results at the three periods of follow-up after LOD
were compared with the pre-operative values (Wilcoxon Signed
Ranks test used). NS ? not significant; *P ? 0.05; **P ? 0.01;
***P ? 0.001. Med.-term ? medium-term.
ovarian volume for both groups of women before treatment
and at medium- and long-term follow-up. The mean ovarian
volume decreased significantly (P ? 0.05) at medium-term
follow-up after LOD and the effect was sustained for up to
9 years. On the other hand, the ovarian volume in the
comparison group did not show significant changes during the
same periods of follow-up.
Factors affecting the endocrinological outcome
The possible impact of age and BMI on the results of the
follow-up was analysed.
by guest on May 29, 2013
Laparoscopic ovarian drilling for PCOS
Figure 3. Ovarian changes in women with PCOS before treatment
and during the three periods of follow-up. The filled columns
represent women who underwent LOD, whereas the open columns
represent women who did not (comparison group). (a) Ultrasound
evidence of polycystic ovaries (PCO): data show the proportion of
women with ultrasound evidence of PCO. 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; medium-term, P ? 0.05; long-term, P ? 0.05. The
results at the two periods of follow-up were compared with
the pre-operative values. NS ? not significant; **P ? 0.01.
(b) Ovarian volume: data show mean values and –1 SD.
Mann–Whitney test was used to compare the two groups before
treatment and during medium- and long-term follow-up periods.
Before treatment, not significant; medium-term, P ? 0.05; long-
term, P ? 0.05. The results at the two periods of follow-up were
compared with the pretreatment values using Wilcoxon signed
ranks test: NS ? not significant; *P ? 0.05.
Age at the time of follow-up had a significant impact on the
serum concentrations of LH after LOD. Women ?36 years old
had significantly (P ? 0.01) lower levels of LH (7.5 IU/l) than
those (10.4 IU/l) of younger (?35 years) women. In contrast,
BMI at the time of long-term follow-up did not appear to have
any significant impact on the serum LH concentrations. In
women with a BMI ?25 kg/m2, the mean serum concentration
of LH was 9.5 IU/l, which was not significantly different to that
of women with a BMI ?25 kg/m2(8.9 IU/l).
impact on the serum concentrations of FSH. Fourteen patients
were aged 39–45 years and their FSH concentrations ranged
between 2.4 and 8.1 IU/l with a mean value of 4.9.
As far as androgen levels are concerned, age did not have a
significant impact on FAI and the serum concentrations of
testosterone and androstenedione at the time of long-term
follow-up. On the other hand, the mean serum concentrations
of testosterone (1.7 nmol/l) and androstenedione (6.5 nmol/l)
in women with BMI ?25 kg/m2were significantly (P ? 0.05)
higher than those of women with BMI ?25 kg/m2(1.2 and
In this study, we report on our observation of the long-term
endocrine and ultrasound changes in 116 anovulatory women
with PCOS after LOD and a comparison group of women
with the same condition, who had not undergone LOD.
We confirm the previously reported endocrine changes shortly
after LOD, including lowering of the LH:FSH ratio and the
serum concentrations of LH and androgens (Gjonnaess, 1984,
1994; Aakvaag and Gjonnaess, 1985; Gjonnaess and Norman,
1987; Greenblatt and Casper, 1987; Sumioki et al., 1988;
Armar et al., 1990; Sakata et al., 1990; Kovacs et al., 1991;
Taskin et al., 1996; Felemban et al., 2000). These endocrine
changes seemed to last during the medium- and long-term
follow-up periods (up to 9 years). This observation is compar-
able with an earlier report by Gjonnaess who demonstrated
that the endocrine changes after LOD were stable for 18–20
years (Gjonnaess, 1998). Naether et al. also showed that serum
testosterone concentrations decreased after LOD and remained
low for up to 6 years (Naether et al., 1994). However, we
confirm in this study that these long-term endocrine changes
are produced by ovarian drilling rather than the effect of
advancing age, since the serum concentrations of LH and
androgens in women who underwent LOD were significantly
lower than those of the comparison group at corresponding
periods of follow-up.
The proportion of women with high LH concentrations
(?10 IU/l) decreased significantly from 70 to 33% shortly
after LOD, but increased back to 45% during the medium-
term follow-up (1–3 years). This latter increase, although
statistically insignificant, shows a trend toward an increase in
serum LH concentrations ?1 year after surgery. One may
therefore speculate that the effect of LOD ‘wore off’ in a
proportion of women (~15%) 1 year after surgery. At long-
term follow-up, the proportion of women with high LH
concentrations decreased to a level (31%) seen at short-term
follow-up after LOD. This latter decrease may be explained
by a phenomenon related to the natural history of the disease,
in that the clinical and endocrine features of PCOS become
less pronounced with advancing age (Dahlgren et al., 1992;
Elting et al., 2000). This is further supported by the observation
that older women (?36 years) at the time of long-term follow-
up had significantly lower serum LH concentrations compared
with younger (?36 years) subjects. However, it appears that
ovarian drilling has contributed to the long-term changes of
serum LH concentrations since the proportion of women with
LH ?10 IU/l at long-term follow-up after surgery were
significantly lower than those of the comparison group during
the corresponding follow-up period. A trend towards a reduc-
tionin theproportion ofwomen withhighserum concentrations
by guest on May 29, 2013
S.A.K.S.Amer et al.
of LH at long-term follow-up was not observed in the compar-
ison group, possibly due to the small number of women
included in that group.
There was a trend toward a decrease of serum androgen
levels with the increasing number of years after LOD, possibly
due to the effect of advancing age (Figure 2). A similar trend
toward a decrease of androgen levels was also observed in the
comparison group; in particular, the significant reduction of
serum androstenedione concentrations at long-term follow-up.
The impact of advancing age on serum concentrations of
androgens was not observed, possibly due to the effect of an
increasing BMI with age, which is associated with an increase
in androgen levels.
In our cohort of patients, there were no cases of premature
ovarian failure (POF) up to 9 years after LOD. At long-term
follow-up, 14 women were aged 39–45 years and their FSH
concentrations ranged between 2.4 and 8.1 IU/l. We can
therefore conclude that using the techniques described in this
study is safe and is not associated with an increased risk of
In this study, we report for the first time on the long-term
impact of ovarian drilling on sonographic features of the
ovaries. Ovarian drilling resulted in a significant reduction in
the ovarian volume and the effect was sustained throughout
the follow-up periods. In one study, Tulandi et al. reported on
the short-term effect of ovarian drilling on the ovarian volume
as measured by three-dimensional (3D) ultrasound (Tulandi
et al., 1997). They found that ovarian drilling resulted in a
transient increase followed by a significant reduction in ovarian
volume from a pre-operative mean value of 12.2 ml to 6.9 ml
3 weeks after surgery. In the present study, we confirm this
reduction in the ovarian volume after ovarian drilling (from
11 to 8.5 ml). In addition, we have shown that this change in
ovarian volume seems to last for up to 9 years.
The mechanism of this reduction of the ovarian volume by
ovarian drilling is not clear. Tulandi et al. measured the volume
of ovarian tissue destroyed by the needle electrode in an
excised ovary using a 3D projection of coloured serial micro-
scopic images (Tulandi et al., 1997). They found that a single
drilling would destroy an average of 0.4 ml of stromal tissue.
They concluded that 10–15 drillings in an ovary would result
in a total tissue destruction of 4–6 ml. This could account for
the observed reduction of the ovarian volume. It may also
explain why the magnitude of reduction of the ovarian volume
in our study (from 11 to 8.5 ml), in which we applied 3–10
punctures per ovary, is smaller than that (from 12.2 to 6.9 ml)
observed by Tulandi et al. who made 10–15 punctures per
ovary (Tulandi et al., 1997). However, it is not clear whether
these findings in an excised ovary can be extrapolated to the
intact ovary. Another possible explanation for the reduction of
ovarian volume is the normalization of ovarian function
produced by ovarian drilling. This is supported by the hypo-
thesis that the typical morphological features of PCOS,
function, e.g. thecal hyperactivity and chronic anovulation
It may be argued that the difference in ovarian volumes
could be the result of inter-observer variability or the use of
different ultrasound machines. These points are unlikely to be
valid, as firstly, earlier studies have demonstrated that real-
time 2D pelvic ultrasonography is a relatively accurate and
reliable method of determining ovarian volume (Campbell
et al., 1982; Goswamy et al., 1988; Higgins et al., 1990).
Secondly, in our unit two similar ultrasound machines have
been used throughout the 9 year follow-up period.
It may also be argued that the reduction of ovarian volume
after ovarian drilling is a sign of excessive ovarian tissue
destruction and could be associated with an increased risk of
ovarian damage and POF. However, as discussed above, in
our cohort of patients there was no POF, even though 14
patients were aged 39–45 years. We can therefore conclude
that this reduction of the ovarian size is a sign of normalization
of ovarian function in women with PCOS, rather than
The long-term beneficial effects of ovarian drilling on
ovarian morphology are further supported by the significant
reduction in the incidence of women with ultrasound evidence
of PCO at medium- and long-term follow-up compared with
the pre-operative level.
In conclusion, our data show that LOD normalizes ovarian
function and morphology in women with PCOS and that these
effects seem to be sustained for up to 9 years in most patients.
We are grateful to all the women who participated in the study. 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.
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Submitted on April 15, 2002; accepted on July 16, 2002
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