Anti-Mullerian Hormone Levels Before and After Ovarian Drilling in Polycystic Ovary Syndrome, Has This An Effect On Fertility 2022

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Javedani Masroor et al.

Reproductive Biology and Endocrinology (2022) 20:129


https://doi.org/10.1186/s12958-022-01002-4

RESEARCH Open Access

Anti‑mullerian hormone levels


before and after ovarian drilling in polycystic
ovary syndrome: has this an effect on fertility?
Mojgan Javedani Masroor1*, Hossein Sheybani2, Shiva Sheybani3 and Nastaran Abolghasem4

Abstract
Background: Polycystic ovary syndrome (PCOS) is the most common endocrine, metabolic, and multi-causal disor-
der in the reproductive period with a possible genetic origin. Women with PCOS are characterized by oligo-ovulation,
clinical or biochemical hyperandrogenism, and polycystic ovaries. Women with PCOS have an increased number of
antral follicles. Anti-Mullerian hormone (AMH), a dimeric glycoprotein produced from the granulosa cells of the pre-
antral and antral follicles, is elevated in PCOS. AMH has been implicated in two stages of follicle dysfunction that lead
to the development of PCOS. The level of AMH decreases following ovarian drilling in patients with PCOS. The present
study compared the level of AMH before and after Laparoscopic ovarian drilling (LOD) in patients with PCOS and its
effect on fertility.
Materials and methods: This cohort study was carried out on 84 women with PCOS who underwent LOD in
Akbarabadi Hospital in Tehran in 2020. Demographic characteristics, AMH, and estradiol levels were determined
before surgery and compared with the amount one week after surgery. The effect of AMH level on pregnancy rate
was also evaluated.
Results: The mean age of the patients was 29.01 ± 4.01 years. The mean Body Mass Index (BMI) of the patients
was 26.33 ± 4.14 kg/m2. The results showed that the mean AMH level decreased significantly after ovarian drilling
(P-value < 0.001). Menstrual cycle distribution was significantly different before and after LOD (P < 0.001). None of the
variables had an effect on the pregnancy (P-value > 0.05). Oligomenorrhea in the previous menstrual period might
cause AMH levels to increase by 3.826 units after LOD (P-value < 0.001).
Conclusion: Measuring serum AMH concentration before treatment can be a useful tool to predict LOD outcomes.
This can help in selecting the patient for treatment.
Trial registration: The project was found to be under the ethical principles and the national norms and standards for
conducting research in Iran with the approval ID and issue date of IR.IUMS.FMD.REC.1397.206 and 2018.08.26 respec-
tively, which has been registered with the research project number 2766 in the Vice-Chancellor for Research and
Technology Development of Iran University of Medical Sciences, School of Medicine, Tehran, Iran. URL: https://​ethics.​
resea​rch.​ac.​ir/​Ethic​sProp​osalV​iew.​php?​id=​34791.
Keywords: Polycystic ovary syndrome, Anti-mullerian hormone, Laparoscopic ovarian drilling

*Correspondence: [email protected]; Introduction


[email protected] Polycystic Ovarian Syndrome (PCOS) with a preva-
1
Shahid Akbar‑Abadi Clinical Research and Development Unit, School lence of about 4–18% is associated with menstrual
of Medicine, Iran University of Medical Sciences, Tehran, Iran
problems, hyperandrogenism, and polycystic ovaries
Full list of author information is available at the end of the article

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Javedani Masroor et al. Reproductive Biology and Endocrinology (2022) 20:129 Page 2 of 6

[1]. PCOS causes approximately 75% of infertility due shown that women with polycystic ovary syndrome
to lack of ovulation [2]. According to a national study, have a 2 to 3 times increase in their serum AMH,
the prevalence of PCOS is 14.2% in Iran [3]. In addition followed by a 2 to 3 times increase in the number of
to infertility, this syndrome is associated with insulin small follicles (2–5 mm) [12, 13]. Increasing the con-
resistance, hyperinsulinemia, hyperandrogenism, fea- centration of AMH affects the pathogenesis of poly-
tures of the metabolic syndrome, and an increased risk cystic ovary syndrome [14]. Studies show that AMH
of diabetes [4]. inhibits the aromatase enzyme, which reduces the
Although the pathogenesis of this disease is com- production of follicular estradiol, and decreased estra-
plex and not fully understood, studies have shown that diol levels may be associated with defects in dominant
androgens and insulin are the main causes of this dis- follicle selection [15].
ease [5]. Insulin has major effects on the ovaries and Numerous studies have shown that nutritional status
the follicles. Hyperinsulinemia is associated with the and obesity can affect AMH synthesis [13–15]. Some
under-developing growth of immature ovarian folli- researchers have reported lower levels of AMH in obese
cles [6]. Increased androgens and an inherent increase women and found an inverse relationship between AMH
in the number of follicles in women with PCOS and body mass index (BMI) [17, 18], while others did not
increase the production of Anti-Mullerian Hormone report a relationship between nutritional factors, BMI,
(AMH) [7]. and AMH [14, 15]. Due to the high level of AMH in the
People with PCOS have higher levels of testoster- patients with PCOS and the possibility of developing
one, insulin, triglycerides, cholesterol, and lutein than ovarian hyperstimulation during infertility treatment in
healthy people. They also have lower levels of sex hor- these patients, we decided to compare the level of AMH
mone-binding globulin (SHBG) and follicular growth before and after Laparoscopic Ovarian Drilling (LOD) in
hormone (FSH) than healthy people [7, 8]. Dyslipi- these patients and its effect on fertility.
demias are also a common finding in PCOS. Other
findings in women with PCOS include an increase in Materials and methods
the prevalence of hypertension, a higher incidence The present study was a cohort study consisting of 84
of atherosclerosis and cardiovascular disease, and women with PCOS who underwent laparoscopic ovar-
an increased risk of myocardial infarction (about 7 ian drilling in Akbarabadi hospital in Tehran in 2020. The
times higher than the healthy people) [5]. The clinical sample size was calculated according to the La Marca
association between hyperinsulinemia and anovula- et al. study [15] and based on the following formula, con-
tion associated with hyperandrogenism is well known sidering alpha as 0.05, d as 0.05, and P as 0.3:
worldwide and among all racial groups [5]. Due to
the physical and mental problems following PCOS in (Z1 − α/2)2 [(P(1 − P)]
women, this disease significantly reduces the quality (d)2
of life [7]. These patients are at risk for various psy-
chological disorders due to metabolic disorders and Inclusion criteria were the PCOS patients based on
especially disorders in the level of sex hormones, the Rotterdam criteria (2003) [16] and candidates for
especially testosterone [8–10]. laparoscopic ovarian drilling treatment. Exclusion cri-
The secretion of AMH decreases gradually during teria were the patients who were not willing to par-
the stages following the growth of the follicle and is ticipate in the study and follow-up visits. AMH and
particularly impossible in follicles larger than 8 mm estradiol levels of the patients were calculated before
[8]. Serum AMH concentration is associated with the surgery and one week after the surgery. Also, the
the number of small follicles, followed by an ovarian success rate of fertility was assessed within the twelve
reserve [9]. Animal studies show that AMH has an months after the surgery, which was indicated by
inhibitory effect on the uptake of primordial follicles, Intrauterine insemination (IUI) or in vitro fertilization
thereby preventing their rapid termination. It has also (IVF).
been shown that AMH reduces the sensitivity of folli-
cles to circulating FSH and can play an important role Ethical considerations
in normal folliculogenesis [10, 11]. During follicular The research followed the Tenets of the Declaration of
growth, when a follicle reaches a certain size (8 mm), Helsinki. This study was approved by the ethics commit-
AMH expression decreases, resulting in an increase in tee of the Iran University of Medical Sciences (IR.IUMS.
the sensitivity of the follicle to circulating FSH, thus, FMD.REC.1397.206). Accordingly, informed consent was
a decrease in AMH levels provides an opportunity for obtained from all the patients.
follicles to grow until ovulation. Previous studies have
Javedani Masroor et al. Reproductive Biology and Endocrinology (2022) 20:129 Page 3 of 6

Table 1 Mean and standard deviation of AMH before and after difference between menstrual cycle distribution
ovarian drilling before and after ovarian drilling (P < 0.001) (Table 2).
Variable Mean Number SD Mean deference P-value The relationship between positive or negative preg-
nancy with age, BMI, AMH, and the menstrual cycle
AMH before LOD 8.8188 78 6.16 3.02 < 0.001 was performed using logistic regression analysis, which
AMH after LOD 5.7936 78 3.65 showed that none of the variables had an effect on preg-
nancy (P> 0.05 (Table 3).
The relationship between mean AMH after drilling
Table 2 Menstrual cycle distribution before and after ovarian with BMI category was investigated using a one-way
drilling analysis of variance. The results showed that the mean
AMH after ovarian drilling was not significantly different
Menstrual cycle After Total
in the BMI categories (P = 0.181) (Table 4).
Regular Oligomenorrhea The relationship between AMH after ovarian drilling
pattern
with the variables of age, BMI, and the previous men-
Before Regular pattern 44 0 < 0.001 strual cycle was examined using linear regression. Age
Oligomenorrhea 18 16 and BMI variables were not significantly associated with
Total 62 16 the previous menstrual cycle (P > 0.05) (Table 5).

Discussion
In the present study, we compared the level of AMH
Statistical analysis before and after laparoscopic ovarian drilling in patients
Descriptive results were presented as mean ± standard with PCOS and its effect on fertility.
deviation (SD) or percentage. An independent t-test was In a prospective cohort study performed by Elmashad
used to compare the two means and in case of abnormal et al., a significant decrease in serum AMH levels of the
data distribution, the Mann–Whitney U test was used. patients with PCOS was observed in the post-treatment
Also, McNemar’s test was used to investigate the dif- phase and the final result indicates the role of AMH
ferences between binary qualitative variables. One-way before laparoscopic ovarian drilling in predicting out-
analysis of variance was used to compare more than two comes [17]. The results of this study were consistent with
means. Logistic regression and linear regression models our study.
were used to control the confounders. A P-value less than In a prospective cohort study performed by Farzadi
0.05 was considered statistically significant. All data were et al. in Iran on 30 women with PCOS who underwent
analyzed using SPSS software version 21. laparoscopic ovarian drilling, it was reported that there
was a significant decrease in the serum AMH level in the
Results post-treatment phase. The mean AMH before treatment
The mean age of the patients was 29.10 ± 4.01 years. The was 8.4 ng/ml, one week, three months, and six months
mean BMI of the patients was 26.33 ± 4.14 kg/m2. Most later were 7.5 ng/ml, 7 ng/ml, and 7.7 ng/ml respectively,
(41%) of the women had normal BMI. The comparison of indicating that this treatment did not cause a change in
mean AMH before and after ovarian drilling was performed ovarian reserve [18].
using paired t-test which showed that the mean AMH after A review study by Amer et al. in the UK on AMH levels
LOD had a significant decrease (P < 0.001) (Table 1). in women with PCOS under laparoscopic ovarian drill-
A comparison of menstrual cycle distribution before ing found a significant reduction in serum AMH levels by
and after ovarian drilling was performed using McNe- 2.13 ng/ml in these patients. In the post-treatment phase,
mar’s test which showed that there was a significant

Table 3 Logistic regression analysis of the relationship between positive or negative pregnancy dimensions with age, BMI, AMH
dimension, and menstrual cycle
Variables B Std. Error (SD) Odds Ratio (OR) 95% Confidence interval P-Value
Lower Upper

Age -0.064 0.079 0.938 0.804 1.095 0.418


BMI 0.048 0.071 1.050 0.913 1.206 0.495
AMH after -0.058 0.087 0.944 0.796 1.120 0.507
Menes after 1.916 1.178 6.794 0.676 68.311 0.104
Javedani Masroor et al. Reproductive Biology and Endocrinology (2022) 20:129 Page 4 of 6

Table 4 Mean AMH after ovarian drilling across BMI category


BMI (kg/m2) Number Mean SD 95% Confidence Interval for Mean P-value
Lower Bound Upper Bound

18.5–25 32 5.13 3.37 3.9156 6.3469 0.181


25–30 31 6.73 4.00 5.2651 8.2058
30–35 15 5.26 3.25 3.4567 7.0633
Total 78 5.79 3.65 4.9695 6.6177

Table 5 Linear regression results to evaluate the relationship between AMH after ovarian drilling with age, BMI, and previous
menstrual cycle
Variables Unstandardized Coefficients 95.0% Confidence Interval P-value
B Std. Error Lower Bound Upper Bound

Constant 3.989 3.271 -2.529 10.506 0.227


Age (year) -0.100 0.091 -0.283 0.082 0.276
BMI (kg/m2) -0.029 0.093 -0.214 0.156 0.754
Previous menstrual cycle 3.826 0.761 2.310 5.343 < 0.001

it is observed that it is not clear whether this reduction It is suggested that the increase in AMH levels in
is only within normal limits, such as in women without patients with PCOS is due to an increase in the num-
PCOS, or reduces ovarian reserve [19]. The results of this ber of primary antral follicles [26]. However, other
study were consistent with the present study. reports have shown that the increase in AMH con-
A study done by Abu Hashim et al. in Egypt on serum centration is mainly due to the increase in AMH
AMH levels in women with PCOS under laparoscopic production by each follicle and is not just the result
ovarian drilling in unilateral and bilateral cases reported of an increase in the number of follicles [27]. AMH
a decrease in serum AMH levels in unilateral and bilat- may be a marker of ovarian aging because it is asso-
eral laparoscopic cases [20]. This study also had consist- ciated with the number of primary antral follicles
ent results with the present study. which indicates the size of the follicle rest chamber,
An analytical study was conducted by Giampaolino so if AMH levels decrease, the ovarian reserve may be
et al. in Italy on 123 women with PCOS under laparo- compromised [28].
scopic ovarian drilling and 123 women with PCOS under The question is whether laparoscopy affects ovar-
Transvaginal hydrolaparoscopy (THL). Both methods ian tissue and reduces ovarian reserve. Weerakiet et al.
showed that the rate of reduction was similar in the two examined changes in serum AMH levels before and after
methods [21]. LOD [29]. They found that the mean changes in serum
In a prospective cohort study conducted by Par- levels of AMH in 21 patients with PCOS were three days
amu et al. in India on 30 women with PCOS under after LOD, which was not statistically significant. In our
laparoscopic ovarian drilling, there was a significant study, mean levels of AMH did not change significantly
reduction of up to 33% in the serum AMH level in before laparoscopy, 1 week, 3 months, and 6 months after
the post-treatment phase [22]. The results of Paramu laparoscopy.
et al. and Gaafar et al.’s studies were consistent with AMH is considered an important marker of ovarian
the present study [22, 23]. reserve [30]. Serum AMH is 2–4 times higher in women
Previous studies have concluded that a decrease in with PCOS than in healthy women. This is because
AMH after LOD should be considered a normaliza- PCOM ovaries show the number of small antral folli-
tion process rather than a pathological decrease in cles producing AMH [31] and increase production in
ovarian reserve. Mild ovarian injury inefficiencies in granulosa cells [32]. An acceptable explanation for the
performing LOD with four to five holes in the ovary decrease in serum AMH after LOD could be the effect
are more effective than performing only two or fewer of heat damage, which reduces its production from the
holes [22, 24, 25].
Javedani Masroor et al. Reproductive Biology and Endocrinology (2022) 20:129 Page 5 of 6

granulosa cells of the primary, pre-abdominal, and small Received: 29 July 2022 Accepted: 23 August 2022
antral follicles [20].

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