Intro
Endometriosis is a common disease affecting about 10% of
women of reproductive age. Ovarian endometriomas could be
found in 17-44% of these patients which shows no symptoms
in up to 50% of the cases ( 1 - 3 ). There is no accurate statistics
in Iran but it seems near to 60% of the infertile couples in Iran
had endometriosis ( 4 ). For many years, the first line therapeutic
approach to these cysts was laparoscopic surgery ( 5 , 6 ). Since
endometriomas lack a true capsule separating the cyst from
the ovarian tissue, it is inevitable to excise the cyst without
cutting some of the normal tissue of the ovary. The point of
question and worrisome in this approach is the damage to the
ovarian reserve as a result of unintentionally excised normal
ovarian tissue ( 7 , 8 ).
Ovarian reserve is a potential predictor of a female’s
reproductive system and is based on the number and
eventual quality of the ovum. In the last three decades,
the level of anti mullerian hormone (AMH) ( 9 ), follicular
stimulating hormone (FSH), estradiol (E2) and inhibin
B as well as the ovarian volume and the antral follicular
count (AFC) on transvaginal sonography have been
accepted as reliable markers of ovarian reserve ( 10 - 12 ),
among which AMH is the most attractive due to its ease
of measurement and independency to the menstrual cycle
( 1 , 13 , 14 ).
Different studies have proved ovarian reserve decline
after laparoscopic excision of endometriomas assessing all
or some of the aforementioned markers. In some studies cyst diameter, cyst bilateralism, preoperative AMH and
patient’s age were shown to be relative to the degree of
ovarian reserve decline. Meanwhile, other studies proved
wise versa ( 15 - 18 ).
This study designed to find any risk factors that make
it possible to predict which patients may have higher
declines in ovarian reserve postoperatively using ovarian
decline rate as a marker showing the degree of the damage
to the ovarian reserve and to give a more precise guide in
cautious choice of patients for laparoscopy.
Results
One hundred patients were included in the study. The
mean ± SD age of the patients and menarche were 29.08
± 4.6 (with a range of 19-41) and 12.56 ± 1.35 years
respectively. The characteristics of the patients with
endometriomas preoperateivley are listed in Table 1 . Also
the frequency of the clinical symptoms and the mean of
BMI and hormonal profiles in the participants are listed
in Table 2 . As seen, dysmenorrhea is the most prevalent
symptom in these women.
AMH levels decreased significantly 3 months after
surgery (P<0.000). The mean ± SD of AMH decline rate
was calculated to be 30.07 ± 2.30% among all patients.
LH levels also declined significantly (P=0.013) but
there were no significant changes between the levels
of FSH pre and postoperatively (P=0.527). There
was no correlation between patients’ charachteristics,
preoperative AMH and CA125 with AMH decline rate
( Table 3 ).
Characteristics of the patients with endometriomas undergoing
laparoscopy (n=100)
*; Calculated in married cases. SD; standard deviation
Frequency of clinical symptoms and the mean of BMI and
hormonal profiles in the participants
*
; Percentage among 100 patients (married and unmarried), **; Percentage among
69 married patients, BMI; Body mass index, FSH; Follicle stimulating hormone, LH;
Luteinizing hormone, CA 125; Cancer antigen 125, and CA 19-9; Cancer antigen 19-9.
Correlation of the rate of AMH decline rate with patient’s
characteristics and lab data
BMI; Body mass index, AMH; Anti mullerian hormone, and CA 125; Cancer antigen 125.
In linear regression please the R and the relations of
other factors with the outcome and their R quantity is
listed in Table 4.
The R square and adjusted R square for the laterality of the
ovarian cyst and hormones
And at last, the multivariate analysis between the
potential predictors and AMH decline rate is shown in
Table 5. As seen just CA 125 (P=0.160) and the grade of
endometriosis (P=0.05) had significant correlation with
AMH decline rate.
Multivariate analysis between the potential predictors and AMH
decline rate
β*
; Unstandardized beta, BMI; Body mass index, AMH; Anti mullerian hormone, and FSH;
Follicular stimulating hormone.
Discussion
Endometriosis is an obscure disease defined by
extrauterine growth of endometrial tissue. Ovaries are
one of the most prevalent sites for endometriosis to be
found. Laparoscopic excision of endometriomas for
long was accepted as the first line therapeutic approach
in these cysts ( 6 , 7 ), but the decreased number of the
ovum's obtained through IVF cycles after endometrioma
cyst excision, gave rise to some worrisome about this
approach ( 19 ).
In the present study, a significant decline in AMH level
as a marker of ovarian reserve was observed three months
postoperatively. This indirectly addresses the inevitable
damage to the ovarian reserve with the surgery of these
cysts. Different characteristics of endometriomas can
lead to ovarian reserve decrease. Indeed, the AMH level
declined postoperatively especially large and bilateral
endometriomas ( 20 ). In another study AMH decreased
significantely at 1, 3 and 6 months after surgery, although,
no difference was detected from preoperative and AMH
values at 12 months ( 21 ). Otherwise, Sugita et al. detected
no significant difference 12 months after surgery ( 22 ).
Also the result of Goodman et al. study was interesting that showed AMH levels have recovered in 12 months
after a transient decrease ( 23 ).
FSH levels did not increase significantly according to
the diminished AMH levels, this has also been explained
in previous studies as FSH seems to be a less sensitive
marker in determining the changes of the ovarian
reserve and its level does not increase significantly until
premenopausal years.
In another study, the only risk factor proved to be
related to the severity of AMH decline rate was the
patients’ preoperative level of AMH, which was not
proved in our study ( 24 ). Indeed, cyst diameter of greater
than 4 centimeters was proved to be a predictor of higher
AMH decline rates postoperatively ( 25 ) and finally cyst
diameter≥7 centimeters, cyst bilateralism, preoperative
AMH level and patients age were introduced to be
effective and relative risk factors for greater decline in
ovarian reserve ( 19 ). Otherwise, none of the mentioned
items were proved in our study.
Regarding the importance of cyst size, in our study, we
found no correlation with AMH decline. However, the
literature is controversial. In one study the decline in AMH
at 6 months after surgery was more evident in the patients
with larger endometriomas (>5 cm) ( 26 ). Otherwise A
meta-analysis showed the greater endometrioma may lead
to the greater damage to ovarian reserves which leads to a
decrease in serum AMH levels ( 27 ).
Regarding the importance of laterality we found no
significant difference in post operative AMH levels in
patients with bilateral compared to unilateral. This is in
line with Suardi et al. study that serum AMH levels were
not influenced by their laterality ( 28 ).
The limitation of our study is the short follow up
duration. Therefore further studies with longer follow up
and investigation of the effect of surgery on the fertility
rate with a focus on AMH are recommended. Also the
non-significant findings in the current study could also be
caused by the small number of the participants.
Conclusions
Since the present study like other studies has shown
a significant decline in AMH levels postoperatively,
while none of the independent variables were found as
a risk factor or predictor of the rate of this decline, we
can conclude that probably surgical intervention even in
patients with the lowest risks can result in diminished
ovarian reserve. This conclusion makes it necessary to
select patients for surgical intervention more cautiously
at any age or with any clinical and paraclinical
presentation.
Materials Methods
This prospective study was conducted in Yas and Arash
Hospitals affiliated to the Tehran University of Medical
Sciences. All participants signed the written informed
consent and were eager to participate in the study.
Women with ovarian endometrioma between 18 to 44
years old who were planned for laparoscopic excision of
the endometrioma between July 2020 and January 2021
were included. The exclusion criteria were a history of
previous adnexal surgery, hormonal replacement therapy,
and endocrine disorder, ovarian mass suspicious for
malignancy, polycystic ovaries and endometriomas of
less than 3 centimeters diameter.
This study was approved by the institutional review
board Tehran University of Medical Sciences (IR.TUMS.
MEDICINE.REC.1399.272). The protocol of the study
was designed according to the ethical principles of
the Declaration of Helsinki. All participants agreed to
participate in the study and the written informed consent
was obtained from all participants.
The sample size that was required with a power of 95 was
70 cases, of which 100 cases were considered for this study.
p1: Preoperative AMH
p2: Postoperative AMH
The demographic (age, weight, height, age of
menarche, marital state) and obstetrical data (gravid and
para), as well as the clinical symptoms (dysmenorrhea,
dyspareunia, persistent pelvic pain, dysphasia, fear
of sex) and history of infertility for female cause were
gathered via a questionnaire that was filled by a physician
or a nursing staff. Also, ultrasound imaging was done for
each patient to see the precise diameter of the cysts and
their laterality status. Patients also underwent laboratory
testing for the level of FSH, LH, AMH, CA125 and CA
19-9 pre and 3 months post operatively.
Also, a new variable was created as AMH decline
rate calculated by the below formula. AMH decline rate
is a new variable to assess any correlation between the
severity of the damage to the ovarian reserve and any of
the other independent variables hypothesized as possible
risk factors.
All the procedures were performed by two expert
laparoscopic surgeons with more than 15 years of
experience in laparoscopic surgery, whose procedures
were to excise the cyst by stripping, avoiding to damage
ovarian normal tissue as much as possible.
All the data were analyzed by the software package for
social sciences (SPSS, IBM, USA) for windows version
15.0. Quantitative values were presented as mean ± SD
and qualitative values were presented as absolute and
relative frequency. Chi-Square test was used to assessed
statistical relations of qualitative variables. Comparison
between the groups was performed using MannWhitney U test. Friedman M test was used to compare
the differences of serum AMH concentrations between
each sampling point and the changes of serum AMH
levels For quantitative variables we used ANOVA and
t test. Also for decreas the potential bias, multivariate
analysis was performed to evaluate the AMH decline
rate with other characteristics. P<0.05 was considered to
be statically significant.
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