Human Reproduction Vol.18, No.8 pp. 1693±1698, 2003
DOI: 10.1093/humrep/deg307
A prospective dose-®nding study of the amount of
thermal energy required for laparoscopic ovarian
diathermy
S.A.K.Amer1, T.C.Li and I.D.Cooke
Department of Obstetrics and Gynaecology, The University of Shef®eld, Jessop Wing, Shef®eld Teaching Hospitals,
Tree Root Walk, Shef®eld S10 2SF, UK
1
To whom correspondence should be addressed. E-mail: s.amer@shef®eld.ac.uk
BACKGROUND: This prospective dose-®nding study was undertaken to determine the optimal amount of
thermal energy required for laparoscopic ovarian diathermy (LOD) in women with polycystic ovary syndrome
(PCOS). METHODS: Thirty women with clomiphene-resistant PCOS were included in the study. All women
underwent LOD. A modi®ed Monte Carlo up-and-down design was utilized. Women were treated in groups of
three (10 groups). The amount of energy applied was standardized at 150 J/puncture. The number of punctures in
each group was decreased/increased according to the number of responders in the previous group. The main
outcome was ovulation as de®ned by a serum progesterone concentration of >30 nmol/l. RESULTS: Four
groups (n = 12) were treated with four punctures/ovary, three groups (n = 9) with three punctures, two groups
(n = 6) with two punctures and one group (n = 3) with one puncture. Ovulation occurred in 67, 44, 33 and 33% of
women treated with four, three, two and one puncture/ovary respectively. The corresponding pregnancy rates
were 67, 56, 17 and 0%. The reductions in the free androgen index and the serum concentrations of testosterone
and androstenedione after LOD were observed only in women treated with three and four punctures/ovary.
CONCLUSION: The clinical response to LOD seems to be dose-dependent, with an increase in the frequency of ovulation and conception with an increasing dose of thermal energy up to 600 J/ovary.
Key words: laparoscopic ovarian drilling/PCOS/polycystic ovary/thermal energy
Introduction
Since the introduction of laparoscopic ovarian diathermy
(LOD) by Gjonnaess (1984) in the early 1980s, LOD has
become widely accepted as a second line treatment for
induction of ovulation in women with polycystic ovary
syndrome (PCOS) after failure of a course of clomiphene
citrate (Armar et al., 1990; Kovacs et al., 1991; Li et al., 1998).
Not only does LOD produce high ovulation (>80%) and
pregnancy (~60%) rates (Li et al., 1998), but it also corrects the
underlying endocrine abnormalities associated with the disease, such as raised serum concentrations of LH and androgens
(Greenblatt and Casper, 1987; Armar et al., 1990; Abdel-Gadir
et al., 1993; Liguori et al., 1996; Felemban et al., 2000). In
addition, ovarian drilling may render the ovaries more sensitive
to clomiphene citrate (Gjonnaess, 1984).
Currently, there is a lack of agreement as to how LOD
should be carried out. The amount of thermal energy applied in
LOD varied markedly (between three and 25 punctures per
ovary at 30±400 W) in different studies (Gjonnaess, 1984;
Dabirashra®, 1989; Weise et al., 1991; Naether et al., 1993;
Felemban et al., 2000). The optimum number of punctures per
ã European Society of Human Reproduction and Embryology
ovary, which determines the amount of energy delivered to
each ovary, has not yet been established. No study has ever
investigated the dose±response relationship in LOD. Gjonnaess
(1984) reported that ovulation occurred more frequently if ®ve
or more punctures were applied compared with three punctures
per ovary. However, Armar et al. (1990) found that four
diathermy punctures per ovary, with a power setting of 40 W,
were suf®cient to achieve good results. On the other hand,
Dabirashra® (1989) suggested that the number of punctures
should be as low as possible and tailored to the individual ovary
in each patient. He reported a case of severe ovarian atrophy
following LOD in which eight punctures were created at
400 W. Weise et al. (1991) noted a positive correlation between
the number of punctures and the reduction in testosterone
levels following LOD.
It seems reasonable to assume that the greater the amount of
injury to the surface of the ovary, the greater also is the risk of
periovarian adhesions. On the other hand, reduction of the
thermal injury may affect the ef®cacy of the procedure.
In this prospective, dose-®nding study, we employed the
modi®ed Monte Carlo up-and-down model with a view to
1693
S.A.K.Amer, T.C.Li and I.D.Cooke
determining the optimal amount of energy required for LOD in
women with PCOS.
Materials and methods
Subjects
Thirty women with anovulatory infertility associated with PCOS were
included in the study. All subjects had polycystic ovaries on
transvaginal ultrasound scan according to criteria de®ned by Adams
et al. (1985). In addition, each woman had biochemical evidence of
PCOS including an elevated LH/FSH ratio (>2) and/or raised serum
concentrations of androgens [testosterone >2.5 nmol/l, androstenedione >10 nmol/l or free androgen index (FAI) >4]. These hormones
were measured in the early follicular phase (de®ned as days 2±5) of
the menstrual cycle. In women with severe oligomenorrhoea or
amenorrhoea, a random blood sample was accepted. FAI is calculated
using the formula testosterone 3 100/sex hormone-binding globulin
(SHBG) (Carter et al., 1983; Eden et al., 1989). All the women in the
study had normal hysterosalpingograms and their partners had normal
semen analysis according to World Health Organization criteria
(WHO, 1999).
All the women had previously failed to respond to incremental
doses of clomiphene citrate (50, 100 and 150 mg). They gave informed
consent for laparoscopic ovarian drilling using diathermy.
Techniques of laparoscopic ovarian drilling
Three-puncture laparoscopy was performed under general anaesthesia. The pelvis was thoroughly inspected for any pathology and the
ovaries were examined for the features of polycystic ovary. A pair of
non-toothed grasping forceps was then used to grasp the utero-ovarian
ligament and to lift the ovary away from the bowel. A specially
designed monopolar electrocautery 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 monopolar 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 probe was applied to the surface of the ovary
at a right angle to avoid slippage and to minimize surface damage. The
electrosurgical unit used was the Force 2 Valleylab electrosurgical
generator (Valleylab Inc., Boulder, CO, USA). A monopolar
coagulating current at a 30 W power setting was used to make a
puncture of ~4 mm diameter and 8 mm depth. As the needle was
pushed into the ovarian capsule, electricity was activated for 5 s. The
ovary was then cooled down by irrigation using Hartmann's solution
before releasing the ligament. At the end of the procedure, ~200 ml of
Hartmann's solution were left in the pelvis.
Amount of thermal energy
A standardized monopolar coagulation current set at 30 W was applied
for a duration of 5 s per puncture, giving a total thermal energy of 150 J
(3035) per puncture.
Monte Carlo up-and-down design
In order to study the dose±response relationship, the Monte Carlo upand-down design was used, utilizing one of the single response
methods reviewed by Bolognese (1983) and modi®ed by Li et al.
(1988). Patients were treated in groups of three (10 groups). The
ovaries were treated with a variable number of punctures (i.e. variable
amount of thermal energy). The number of responders in each group
governed the amount of thermal energy in the next group, as follows:
if the number of responders = 3, the number of punctures would be
reduced by two; if the number of responders = 2, the number of
1694
punctures would be reduced by one; if the number of responders = 1,
then the number of punctures would be increased by one; if the
number of responders = 0, then the number of punctures would be
increased by two. For instance, when four punctures/ovary are applied
in a certain group, if all the three patients in this group respond
positively, the next group would be treated with two punctures/ovary.
If two patients respond to four punctures, the number of punctures will
be reduced to three punctures/ovary, and if the number of responders
is one, the next group will receive ®ve punctures/ovary. If four
punctures result in no response at all, the number of punctures will
increase to six punctures/ovary. A positive response was de®ned when
there was endocrinological evidence of ovulation, i.e. progesterone
>30 nmol/l. The amount of thermal energy used in the ®rst group was
four punctures (i.e. 600 J) per ovary, i.e. 1200 J per subject.
Post-operative monitoring
Following ovarian diathermy, blood samples were taken weekly to
measure the serum concentrations of progesterone until menstruation
occured or a level of >30 nmol/l was detected. 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 if any
of the progesterone concentrations was >30 nmol/l. If spontaneous
menstruation did not occur, a random blood sample was taken to
measure all the above hormones at 6 weeks following surgery. If the
patient did not ovulate as evidenced by the low progesterone levels or
lack of menstruation, clomiphene citrate would be started 6±8 weeks
after surgery.
Ethical issues
The South Shef®eld Ethics Committee approved this study. All the
women participating in the study gave an informed consent.
Statistical analysis
Endocrine parameters before and after LOD were compared using
Wilcoxon signed rank tests. P < 0.05 was considered signi®cant.
Contingency table analysis was used to compare success rates after
LOD across different body mass index (BMI) groups and different
menstrual cycle groups.
Results
The characteristics of the 30 women participating in this study
are illustrated in Table I.
Dose ranging
The results of the treatment are illustrated in Table II. Four
groups of patients (n = 12) were treated with 600 J
(four punctures) per ovary, three groups (n = 9) with 450 J
(three punctures) per ovary, two groups (n = 3) with 300 J (two
punctures) per ovary and one group (n = 3) with 150 J
(one puncture) per ovary.
Ovulation
Figure 1a shows the rate of spontaneous ovulation achieved
using different doses of thermal energy. The incidence of
spontaneous ovulation was 67% (8/12) for 600 J per ovary,
44% (4/9) for 450 J, 33 (2/6) for 300 J and 33% (1/3) for 150 J.
After administering clomiphene citrate to women who did not
Dose-®nding study of laparoscopic ovarian diathermy
Table I. The characteristics of 30 women who had laparoscopic ovarian
drilling for anovulatory infertility due to POCS
Characteristic
Results
Age (years)
BMI (kg/m2)
Duration of infertility (years)
Serum LH (IU/l)
Serum FSH (IU/l)
Serum LH/FSH ratio
Serum testosterone (nmol/l)
Serum androstenedione (nmol/l)
Free androgen index
Menstrual cycle pattern
Regular
Oligomenorrhoea
Amenorrhoea
Hirsutism
Yes
No
Acne
Yes
No
Infertility
Primary
Secondary
29.6 [4.5]
26.8 [5.5]
2.6 [1.1]
13.8 [6.2]
5.2 [1.1]
2.7 [1.2]
2.3 [1.3]
9.6 [4.1]
6.3 [5.0]
3 (10)
19 (63)
8 (27)
3 (10)
27 (90)
3 (10)
27 (90)
16 (53)
14 (27)
Values are given as mean [SD] and n (%).
Table II. The results of Monte Carlo up-and-down dose ®nding in the
study of LOD for PCOS
Group
1
2
3
4
5
6
7
8
9
10
Dose of thermal energy
No. of responders
No. of punctures
per ovary
Energy
per ovary (J)
4
3
4
3
2
1
2
4
3
4
600
450
600
450
300
150
300
600
450
600
2
1
2
2
2
1
0
2
1
2
ovulate spontaneously, the ovulation rates increased to 92, 78,
83 and 67% in women treated with a total dose of 600, 450, 300
and 150 J per ovary respectively. The overall rate of ovulation
was 80% (24/30).
Conception
Figure 1b shows the conception rates achieved with different
doses of thermal energy during the ®rst year after surgery.
Amongst the 12 women treated with 600 J (four punctures) per
ovary, eight (67%) conceived. Of the nine women treated with
450 J, ®ve (56%) conceived, and of the six women treated with
300 J, one (17%) conceived. There were no conceptions
amongst the three women treated with 150 J. Overall, amongst
the 30 women in this study, 14 (47%) conceived within 12
months after surgery. Amongst the 14 pregnancies achieved,
Figure 1. The rates of spontaneous ovulation, conception and
conversion of oligo/amenorrhoea to regular cycles in women with
PCOS after laparoscopic ovarian diathermy (LOD) using different
doses of thermal energy (numbers of punctures).
two (14%) ended in miscarriages, one was terminated for social
reasons and the remaining 11 pregnancies continued to full
term. The two miscarriages occurred in women treated with
450 J per ovary.
Menstrual pattern
As shown in Figure 1c, the rate of conversion from oligo/
amenorrhoea to regular menstrual cycles after ovarian
diathermy is higher in women treated with 600 and 450 J (73
and 75%), respectively, compared with those treated with 300
and 150 J (33 and 50%) respectively.
Endocrine changes
The endocrine changes after ovarian diathermy, using different
amounts of thermal energy, are shown in Table III. In view of
the small number of patients treated with 150 J/ovary, they
1695
S.A.K.Amer, T.C.Li and I.D.Cooke
Table III. Endocrine changes after LOD in 30 women with anovulatory infertility due to PCOS
(a) Changes in the serum concentrations of gonadotrophins after LOD
Punctures
per ovary
LH (IU/l)
Pre-op
Post-op
Pre-op
Post-op
Pre-op
Post-op
1±2
18.5
(8.3±24.3)
16.8
(2.8±23.7)
10.7
(6.3±18.9)
12.7
(2.8±24.3)
6.8
(2.0±20.9)
5.6
(4.2±7.2)
7.0*
(2.1±15.2)
6.5**
(2.0±20.9)
5.2
(2.3±6.7)
5.8
(4.2±7.2)
4.8
(3.7±6.1)
5.5
(2.3±7.2)
5.1
(4.6±7.4)
5.9
(4.5±9.0)
4.7
(3.0±6.0)
5.3
(3.0±9.0)
3.6
(1.5±5.3)
2.9
(0.5±4.0)
2.4
(1.4±3.8)
2.8
(0.5±5.3)
1.2
(0.3±4.5)
1.0
(0.5±3.3)
2.0*
(0.6±2.6)
1.2**
(0.3±4.5)
3
4
Overall
FSH (IU/l)
LH/FSH ratio
(b) Changes in the serum concentrations of androgens after LOD
Punctures
per ovary
T (nmol/l)
Pre-op
Post-op
Pre-op
Post-op
Pre-op
Post-op
Pre-op
Post-op
1±2
1.4
(0.8±5.1)
2.7
(0.7±2.9)
2.5
(0.8±4.0)
2.4
(0.7±5.1)
2.1
(1.1±3.1)
1.7
(1.2±2.8)
1.9
(0.7±3.7)
1.9
(0.7±3.7)
7.9
(4.7±19.2)
9.2
(3.3±10.8)
9.9
(6.2±16.0)
8.7
(3.3±19.2)
8.8
(1.0±18.6)
5.8
(5.1±6.6)
9.0*
(3.5±13.5)
6.6**
(1.0±18.6)
3.7
(1.0±11.4)
7.1
(1.3±20.3)
7.4
(1.7±14.1)
6.2
(1.0±20.3)
3.6
(2.8±6.1)
5.0
(2.2±19.6)
4.7
(0.8±9.8)
4.1*
(0.8±19.6)
51.8
(29.7±81.7)
38
(14.3±53.5)
37.1
(20.5±82.0)
43.0
(14.3±82.0)
52.5
(38.8±57.0)
32.8
(23.5±55.0)
47.3
(29.9±122.0)
37.3
(23.5±122.0)
3
4
Overall
A (nmol/l)
FAI
SHBG (nmol/l)
Values are given as median (range). Wilcoxon signed ranks test was used to compare the pre-and post-operative values (*P < 0.05, **P < 0.01).
T = testosterone; A = androstenedione; SHBG = sex hormone-binding globulin; FAI = free androgen index.
were combined with patients receiving 300 J/ovary to allow
statistical analysis.
The overall results showed a statistically signi®cant
(P < 0.01) reduction of the median serum concentration of
LH from 12.7 IU/l pre-operatively to 6.5 IU/l after LOD
(Table IIIa). Similarly, the LH/FSH ratio signi®cantly (P < 0.01)
decreased from 2.8 to 1.2. Although, the serum concentrations
of LH and the LH/FSH ratio decreased in all groups, statistical
signi®cance (P < 0.05) was only obtained in women treated
with the highest dose (600 J/ovary). However, there is no
obvious correlation between the number of punctures and the
magnitude of changes of these hormones. There were no
signi®cant changes in the serum FSH levels after ovarian
diathermy in women treated with 600, 450 or 300/150 J
respectively (Table IIIa).
With regard to the androgens, the results in Table IIIb show a
reduction of FAI and the serum concentrations of testosterone
and androstenedione after LOD in women receiving higher
doses of thermal energy (450 and 600 J). However, these
changes did not reach statistical signi®cance, except for
androstenedione. On the other hand, the levels of these
hormones showed a trend towards a small, but statistically
insigni®cant, increase after LOD in women treated with 150
and 300 J/ovary. The changes in the serum concentrations of
SHBG were variable and statistically insigni®cant.
The impact of BMI and menstrual pattern on the outcome
of LOD
The success rates after LOD were compared between women
with normal (<28 kg/m2), moderately elevated (28±32 kg/m2)
and markedly elevated BMI (>32 kg/m2) using contingency
1696
table analyses. Similarly, success rates were compared between
women with regular menstrual cycles, oligomenorrhoea and
amenorrhoea. The results showed a trend towards a higher
ovulation rate (59%) in women with normal BMI (n = 17)
compared with ovulation rates of 37 and 40% in women with
moderately elevated (n = 8) and markedly elevated BMI (n = 5)
respectively. However, the differences did not reach statistical
signi®cance. The corresponding pregnancy rates were 53, 37
and 40%. Women with oligomenorrhoea (n = 19) showed a
higher ovulation rate (63%) compared with that (33 and 25%)
of women with regular cycles (n = 3) and amenorrhoea (n = 8),
respectively, but statistical signi®cance was not achieved. The
corresponding pregnancy rates were 59, 33 and 25%.
Comparison between the demographic characteristics of the
four groups of women receiving different numbers of punctures
at LOD showed no statistically signi®cant differences in age,
BMI or menstrual pattern.
Discussion
In this study, we employed the Monte Carlo up-and-down
design, in 30 women with anovulatory PCOS to investigate the
dose±response relationship of LOD.
Monte Carlo up-and-down design
The concept of the up-and-down design for dose ®nding, which
was ®rst introduced by Bliss (1935) and later reviewed by
Bolognese (1983), involves assigning each subject's dose
based on the previous observation. If the previous observation
was a non-response, then the dose is increased according to a
pre-chosen dosage increment. If the previous observation was a
Dose-®nding study of laparoscopic ovarian diathermy
response, then the dose is decreased to the next lower level.
With such an approach, the doses will migrate toward/within
the effective dose range, according to the prede®ned response,
i.e. between the threshold dose (the lowest level at which a
subject will respond) and the plateau dose (the lowest dose
such that all subjects who will respond are observed to
respond). Several up-and-down designs have been described
depending on the nature of the therapeutic method being
investigated, e.g. the design involving one observation of each
of 30 subjects or observations in a group of three subjects in 10
groups. In the latter case, the dose will be decreased or
decreased based on the number of responders in the preceding
group. The increment could be doubled if, for example, all
subjects in the preceding group responded or did not respond.
The latter design has been chosen for this study as it suited the
nature of the treatment (ovarian diathermy).
The number of subjects in this study was chosen to be 30 as
this number has been considered by many authors to be enough
to produce meaningful results (Bolognese, 1983). The dose of
thermal energy used in the ®rst group was chosen based on the
available evidence from a previous report by Armar et al.
(1990) who found that four diathermy punctures per ovary
were suf®cient to achieve good results.
delivered the thermal energy to a depth of 2±4 mm, i.e.
super®cially, required a high amount of energy to achieve good
results. In contrast, with deeper penetration of the ovarian
surface using the diathermy needle (Rocket of London,
Watford, UK), we achieved good results with a much lower
energy requirement. Our results are consistent with the ®ndings
of Armar et al. (1990) who used a similar instrument.
Similarly, Felemban et al. (2000), using a diathermy needle,
delivered the energy to a depth of 8 mm and achieved good
success rates with amounts of thermal energy
(40 W 3 2 s 3 10±15 = 800±1200 J per ovary) much lower
than that applied by Gjonnaess (1984). It is therefore possible
to conclude that deeper penetration of the ovarian surface
during LOD allows signi®cant reduction of the amount of
thermal energy without compromising the outcome.
Dose±response relationship
In a previous retrospective study, we have demonstrated that
increasing the number of punctures to more than three (up to
10) punctures/ovary does not result in a signi®cant improvement in the success rates (Amer et al., 2002). It can therefore
be concluded that 3±4 punctures (450±600 J) per ovary
represent the optimum dose of energy required for LOD, i.e.
reducing the dose below that level is associated with poorer
results and increasing the dose above it does not improve the
outcome.
We have demonstrated in this study, for the ®rst time, that the
response to LOD is governed by a dose±response relationship.
As illustrated in Figure 1a, the frequency of spontaneous
ovulation after ovarian diathermy increases with an increase in
the amount of thermal energy up to 600 J (four punctures) per
ovary. Furthermore, there was a tendency for the dose of
thermal energy to move from 150 toward 600 J, resulting in
four groups (12 subjects) being treated with 600 J and only one
group (three subjects) receiving 150 J. This indicates that 150 J/
ovary could be the threshold dose, i.e. the lowest dose at which
a response could be seen, and 600 J/ovary may be the plateau
dose, i.e. the lowest dose at which all subjects who will respond
are observed to respond.
When clomiphene citrate was later given to the nonresponders, the incidence of ovulation increased in all groups
and did not show a dose±response relationship. This indicates
that a small dose of thermal energy, e.g. two punctures (300 J),
only may be suf®cient to sensitize the ovary to clomiphene
citrate.
Two previous studies reported on the relationship between
the number of punctures made during LOD and the success
rates. Gjonnaess (1984) found that better results were achieved
when ®ve or more punctures (2±4 mm deep) were made in each
ovary at 200±300 W for 2±4 s each puncture (energy on
average = 250 W 3 3 s 3 >5 = > 3750 J per ovary). On the
other hand, Armar et al. (1990) found that four diathermy
punctures (8 mm deep) per ovary at 40 W for 4 s per puncture
(energy = 40 W 3 4 s 3 4 = 640 J) were suf®cient to achieve
good results. The discrepancy between our results and those
reported by Gjonnaess (1984) could be explained by the
differences in the techniques of LOD, in particular the
instrument used and the depth of penetration. Gjonnaess
(1984), using the biopsy or sterilization forceps, which
Conceptions and menstrual pattern
The dose±response relationship was con®rmed further by the
conception rate and the conversion to regular menstrual
patterns after ovarian diathermy, which showed an increase
with the increase in the amount of thermal energy (Figure 1b
and c).
The optimal amount of thermal energy for LOD
Distribution of the total amount of thermal energy
Having identi®ed the optimum amount of thermal energy to
be delivered to the ovarian stroma at LOD, the optimal
distribution of that dose of energy remains to be evaluated.
Balen and Jacobs (1994) compared unilateral with bilateral
ovarian diathermy in 10 patients with anti-estrogen-resistant
PCOS. They reported a 75% ovulation rate in women who
underwent unilateral ovarian diathermy applying four punctures using 40 W for 4 s, i.e. 640 J. They also found that
unilateral ovarian diathermy resulted in ovulation from the
contralateral ovary in the ®rst cycle and then alternatively
from each ovary. Although the numbers in this study are
small, it clearly indicates that the effects of LOD depend on
the destruction of a certain amount of ovarian tissue, whether
this is in¯icted on one ovary or divided between the two
ovaries. It is therefore possible that the optimal amount of
energy could be delivered to one ovary only without
compromising the success rates. The potential bene®t of
such an approach in minimizing post-operative adhesion
formation requires further evaluation.
Endocrine changes
Numerous previous studies have shown that LOD results in
a fall in the serum levels of androgens and LH (Aakvaag
1697
S.A.K.Amer, T.C.Li and I.D.Cooke
and Gjonnaess, 1985; Greenblatt and Caspor, 1987; AbdelGadir et al., 1993; Naether et al., 1993; Liguori et al.,
1996; Felemban et al., 2000; Amer et al., 2002). In this study,
the reduction of the serum LH concentrations was observed
with all the doses of thermal energy. The magnitude of
reduction of LH did not show any dose dependency. Statistical
signi®cance was only observed in the group of women treated
with 600 J. The lack of statistical signi®cance in the other
groups may be due to the small numbers of patients included.
The exact mechanism of LH reduction after LOD is still not
fully understood.
On the other hand, the reductions of FAI and the serum
concentrations of testosterone and androstenedione after LOD
were only observed in women receiving higher doses of
thermal energy (450 and 600 J). It may therefore be concluded
that the effect of LOD on the androgen levels is in¯uenced by
the amount of energy delivered to the ovary, and a small
amount may not reduce these levels. It is also observed that the
reduction of androgens was associated with higher success
rates in the two groups treated with higher amounts of energy.
This may support the hypothesis that LOD works by the
destruction of androgen-producing tissue in the ovary. The
resulting fall of the serum androgen concentrations may result
in a fall in estrone (E1) concentrations due to decreased
peripheral aromatization of androgens. It has been speculated
that this fall in E1 is responsible for decreased positive
feedback on LH and decreased negative feedback on FSH at
the level of the pituitary.
The impact of BMI and menstrual pattern on the outcome
of LOD
Our data showed that PCOS women with normal BMI and
those with oligomenorrhoea have a tendency to respond better
to LOD than women with higher BMI and amenorrhoea. The
lack of statistical signi®cance may be due to the small numbers
in each group. This will therefore need to be evaluated further
in a larger group of patients. There were no statistically
signi®cant differences in the BMI and menstrual patterns
between the four groups of women. It is therefore unlikely that
the differences in the outcome of LOD observed between the
four groups in this study are due to variations in BMI or
menstrual pattern.
Conclusion
In conclusion, we have demonstrated that the clinical and
endocrine response to LOD is governed by a dose±response
relationship. Four punctures per ovary using a power
setting of 30 W for a duration of 5 s per puncture (i.e.
600 J per ovary) appear to be suf®cient to produce an
optimal response (67% spontaneous ovulation rate and 67%
conception rate). Reducing the thermal energy below that
level reduces the chances of spontaneous ovulation, and
conception.
1698
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Submitted on November 4, 2002; accepted on April 15, 2003