Improvement and effect of stress responses and ovarian reserve function in patients with ovarian cysts after laparoscopic surgery.

Introduction

Ovarian cysts are a common gynecological benign tumor. In recent years, with changes in social life and eating habits, the incidence rate of ovarian cysts has steadily increased. Women must maintain normal reproductive endocrine processes to reproduce. Therefore, ovarian cysts cause adverse effects on women’s endocrine system and then cause infertility. Therefore, ovarian cysts pose a serious threat to the health of women.[1,2] Surgery has been the main effective treatment for ovarian cysts for a long time because of the high degree of deterioration of ovarian cysts. However, traditional laparotomy not only causes trauma to the patient’s body and adversely affects ovarian function, but also causes various stress responses in patients. All of the above-mentioned effects are not conducive to postoperative recovery of patients.[3] In recent years, with continuous development of technology and minimally invasive techniques, laparoscopic surgery has been gradually applied for treating various diseases as a method with a small amount of trauma, rapid recovery, and minimal complications.[4] Many studies have shown that application of laparoscopy in ovarian cyst dissection has achieved good results, and patients who receive laparoscopy recover faster postoperatively than those who receive traditional laparotomy.[5,6]

However, some studies have shown that although laparoscopic surgery can reduce the damage caused by surgery in the ovaries and the body compared with traditional laparotomy, it still affects the patient’s ovarian reserve function and stress response.[7] Ovarian reserve function refers to the ability of follicles to form fertilized oocytes in the ovarian cortex. When the ovarian reserve function is reduced, the follicles remaining in the ovary will also decrease and the quality of the follicle will decrease, eventually leading to ovarian failure.[8] The stress response is an important index for evaluating the effect of surgery, and it can be used for objective evaluation of the adverse effects of surgery.[9] This has important clinical significance for monitoring of surgical effects.

However, little is known regarding the effects of laparoscopic surgery on the patient’s stress response and ovarian reserve function. Therefore, this study aimed to analyze the effects of different surgical procedures on the postoperative stress response and ovarian reserve function in patients with ovarian cysts. We separately collated and compared clinical data of abdominal ovarian cyst dissection and laparoscopic ovarian cyst dissection of ovarian cysts.

Methods

Patients

A retrospective analysis was performed on 117 patients with ovarian cysts in our hospital. Among them, there were 34 cases with teratoma, 41 cases with chocolate cysts, and 42 cases with simple ovarian cysts. Among them, 51 patients who underwent ovarian cyst dissection via abdomen were in the control group, and 66 patients who underwent ovarian cyst dissection via laparoscopy were in the experimental group. Patients who were diagnosed with ovarian cysts by imaging were included. Exclusion criteria were as follows: patients with severe liver and kidney dysfunction; patients with severe organ disease or tumors; patients with coagulopathy; patients with surgical contraindications; patients with cognitive and communication disorders; patients with severe infectious diseases; and patients who did not cooperate with the experiment. All patients and their families agreed to participate in the experiment and signed the informed consent form. This experiment was approved by the ethics committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University Reproductive Center.

Experimental methods

All patients underwent general anesthesia with endotracheal intubation and routine preoperative preparation, such as enema. The patients were divided into two groups. The control group underwent traditional ovarian cyst dissection via the abdomen. Patients were placed in the lithotomy position. During the surgery, lesions were detected by conventional abdominal incision and cyst dissection was performed. Double-click electrocoagulation was used to stop bleeding and suturing was performed after surgery. The experimental group underwent laparoscopic cystectomy. Patients in this group were also placed in the lithotomy position. A longitudinal incision of approximately 10 mm was made in the umbilicus, and a laparoscope was placed through the incision to establish CO2 pneumoperitoneum to maintain intraabdominal pressure below 15 mmHg. After detection of ovarian lesions, the diseased ovaries were fixed, and the ovarian cortex and cysts were bluntly separated. The cyst was peeled off by the tearing method, and the cyst was prevented from being broken during the peeling process. Rinsing with physiological saline solution was performed while peeling off. After the cyst was completely peeled off, the wound was washed and sutured after washing. A specimen bag was placed into the abdominal cavity, and the dissected cyst was placed into the bag and removed from the incision in the umbilicus. Finally, a drainage tube was placed, the lens body and cannula were removed, and the wound was sutured after removal of CO2 gas.

Measurement outcomes

The operation time and intraoperative blood loss of the two groups were recorded and compared. Ovarian reserve function was then recorded before treatment and 1 month after treatment, including serum ovarian function-related indices and stress indices. Serum ovarian function-related indices included estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and inhibin B (INHB). Stress indices included serum cortisol, high-sensitivity C-reactive protein (hs-CRP), and norepinephrine (NE).

Statistical methods

Measurement data are expressed as mean ± standard deviation. The t test was used for comparison between the two groups and the chi-squared test was used for count data. SPSS 18.0 software (Bo Yi Zhixun Information Technology Co., Ltd. Beijing, China) was used for statistical analysis of the data. P < 0.05 indicates a statistically significant difference.

Results

General characteristics of the patients

The mean age of the patients was 41.57 ± 3.22 years. There were no significant differences in the patients’ characteristics, including age, body mass index, and ovarian cyst types, between the two groups (Table 1).

Table 1.

Patients’ characteristics.

Variable	Experimental group, n = 66	Control group, n = 51	t/χ2	P
Age (years)			0.000	0.977
≥40	39 (59.09)	30 (58.82)
<40	27 (40.91)	21 (41.18)
BMI (kg/m2)			0.000	0.987
≥23	41 (62.12)	31 (60.78)
<23	25 (37.88)	20 (39.22)
Drinking history			0.078	0.780
Yes	21 (31.82)	15 (29.41)
No	45 (68.18)	36 (70.59)
Type of cyst			0.126	0.939
Teratoma	19 (28.79)	15 (29.41)
Chocolate cyst	24 (36.36)	17 (33.33)
Simple ovarian cyst	23 (34.85)	19 (37.25)
Coagulation function
Activated partial thromboplastin time (s)	28.12 ± 2.09	28.23 ± 2.11	0.281	0.779
Prothrombin time (s)	11.87 ± 1.21	11.98 ± 1.09	0.509	0.612
Fibrinogen (g/L)	3.21 ± 0.25	3.19 ± 0.23	0.444	0.658
Thrombin time (s)	14.56 ± 1.58	14.57 ± 1.61	0.034	0.973
Cyst diameter	7.25 ± 1.17	7.29 ± 1.18	0.183	0.855
Renal function indices (µmol/L)
Creatinine	63.67 ± 4.11	62.97 ± 4.07	0.917	0.361
Urea	5.56 ± 0.81	5.64 ± 0.79	0.536	0.593
uric acid	289.14 ± 11.59	291.15 ± 12.06	0.914	0.913

Values are mean ± standard deviation or n (%).

BMI: body mass index; s: seconds.

Comparison of surgical conditions between the two groups

Mean intraoperative blood loss, operation time, and time to get out of bed in the experimental group were significantly less than those in the control group (all P < 0.001) (Table 2). These findings indicated that the operation and recovery in the experimental group were better than those in the control group.

Table 2.

Comparison of operative conditions between the two groups.

Variable	Experimental group, n = 66	Control group, n = 51	t	P
Intraoperative blood loss (mL)	46.57 ± 7.45	84.29 ± 11.37	21.62	<0.001
Operation time (min)	41.78 ± 7.12	68.05 ± 9.22	17.40	<0.001
Time to get out of bed (hours)	32.81 ± 6.93	45.26 ± 10.41	7.749	<0.001

Values are mean ± standard deviation.

FSH, LH, E2, AMH, and INHB levels before and 1 month after the operation in the two groups

There were no significant differences in preoperative ovarian reserve function between the two groups (Table 3). One month after surgery, FSH, LH, and AMH levels in the experimental group were significantly lower than those in the control group (all P < 0.05). E2 and INHB levels in the experimental group were significantly higher than those in the control group (both P < 0.001) (Table 4, Figure 1). These findings indicated that laparoscopic surgery had less effect on ovarian reserve function indices than did traditional laparotomy.

Table 3.

Preoperative ovarian reserve function in the two groups.

Variable	Experimental group, n = 66	Control group, n = 51	t	P
FSH (mIU/mL)	18.56 ± 1.82	18.63 ± 1.84	0.205	0.838
LH (mIU/mL)	17.29 ± 1.56	17.41 ± 1.34	0.438	0.662
E2 (pg/mL)	172.11 ± 40.83	172.07 ± 42.12	0.005	0.996
AMH (pg/mL)	4.85 ± 0.67	4.76 ± 0.63	0.739	0.461
INHB (ng/mL)	53.17 ± 15.33	52.98 ± 15.42	0.739	0.461

Values are mean ± standard deviation. FSH: follicle-stimulating hormone; LH: luteinizing hormone; E2: estradiol; AMH: anti-Müllerian hormone; INHB: inhibin B.

Table 4.

Ovarian reserve function in the two groups 1 month after the operation.

Variable	Experimental group, n = 66	Control group, n = 51	t	P
FSH (mIU/mL)	22.27 ± 1.92	27.73 ± 1.88	15.39	<0.001
LH (mIU/mL)	19.29 ± 1.56	25.41 ± 1.34	22.35	<0.001
E2 (pg/mL)	167.16 ± 13.34	145.42 ± 12.15	9.084	<0.001
AMH (pg/mL)	3.05 ± 0.45	3.37 ± 0.53	3.529	<0.050
INHB (ng/mL)	23.46 ± 1.84	19.82 ± 1.93	10.39	<0.001

Values are mean ± standard deviation. FSH: follicle-stimulating hormone; LH: luteinizing hormone; E2: estradiol; AMH: anti-Müllerian hormone; INHB: inhibin B.

Figure 1.

The outcomes of ovarian reserve function were compared between the two groups 1 month after surgery. Change in ovarian reserve function indices were significantly less in the experimental group than in the control group (P < 0.05). Note: *P < 0.05.

Maximum diameter of the ovary and the number of antral follicles before and after surgery in the two groups

Before surgery, there were no significant differences in the maximum diameter of the ovary and the number of antral follicles between the two groups (Table 5). One month after surgery, the maximum diameter of the ovary and the number of antral follicles in the experimental group were significantly less than those in the control group (both P < 0.001) (Table 6, Figure 2).

Table 5.

Maximum diameter of the ovary and the number of antral follicles before the operation in the two groups.

Variable	Experimental group, n = 66	Control group, n = 51	t	P
Maximum diameter of the ovary (cm)	51.47 ± 2.49	52.12 ± 2.38	1.427	0.156
Number of sinus follicles	6.46 ± 1.11	6.42 ± 1.13	0.192	0.848

Values are mean ± standard deviation.

Table 6.

Maximum diameter of the ovary and the number of antral follicles after the operation in the two groups.

Factor	Experimental group, n = 66	control group, n = 51	t	P
Maximum diameter of the ovary (cm)	19.59 ± 1.81	22.56 ± 2.31	7.799	<0.001
Number of sinus follicles	4.57 ± 0.68	6.15 ± 1.09	9.608	<0.001

Values are mean ± standard deviation.

Figure 2.

The maximum diameter of the ovary and the number of antral follicles in the experimental group were less than those in the control group (P < 0.05). Note: *P < 0.05.

Comparison of stress indices before and after treatment in the two groups

There were no significant differences in the levels of stress indices between the two groups before surgery (Table 7). Cortisol, NE, and hs-CRP levels were significantly lower in the experimental group than in the control group 1 month after surgery (all P < 0.001). (Table 8, Figure 3). These findings indicated that laparoscopic surgery had less effect on stress indices of patients than did laparotomy.

Table 7.

Levels of cortisol, NE, and hs-CRP before treatment in the two groups.

Factor	Experimental group, n = 66	Control group, n = 51	t	P
Cortisol (ng/mL)	192.79 ± 16.26	191.98 ± 16.31	0.267	0.790
NE (ng/mL)	239.55 ± 20.06	238.91 ± 20.85	0.168	0.867
hs-CRP (mg/mL)	4.67 ± 0.54	4.61 ± 0.55	0.591	0.556

Values are mean ± standard deviation.

NE: norepinephrine; hs-CRP: high-sensitivity C-reactive protein.

Table 8.

Levels of cortisol, NE, and hs-CRP after treatment in the two groups.

Factor	Experimental group, n = 66	Control group, n = 51	t	P
Cortisol (ng/mL)	206.41 ± 19.83	245.29 ± 21.59	8.141	<0.001
NE (ng/mL)	272.73 ± 22.85	309.39 ± 27.89	7.814	<0.001
hs-CRP (mg/mL)	5.37 ± 0.69	7.86 ± 1.13	14.71	<0.001

Values are mean ± standard deviation.

NE: norepinephrine; hs-CRP: high-sensitivity C-reactive protein.

Figure 3.

Changes in stress response indices after surgery in the two groups. Changes in the ovarian stress response in the experimental group were significantly less than those in the control group after surgery (P < 0.05). Note: *P < 0.05.

Discussion

Ovarian cysts are a common genital disease in women and often cause symptoms, such as menstrual disorders and infertility, which have serious adverse effects on women’s physical and mental health.[10] Surgical treatment is the main treatment of ovarian cysts. For ovarian cysts, although traditional laparotomy has good efficacy, the prognosis of patients after surgery is still poor because of its large incision, slow wound recovery, and postoperative infections and complications.[11,12] In recent years, with the development of medical science and technology, laparoscopy has been widely used for various diseases, including gynecology. Laparoscopic surgery has gradually become the preferred treatment for ovarian cysts because of the small amount of trauma, rapid recovery and ability to meet the aesthetic requirements of patients.[13,14] Studies have also shown that laparoscopic surgery not only protects ovarian reserve function better than traditional laparotomy, but it also has less surgical trauma and stress responses than conventional open surgery.[15,16] A large number of studies[17,18] have suggested that AMH and INHB levels can be used as relatively direct indices of ovarian reserve function. Other studies[19] have shown that FSH, LH, and E2 levels have a good correlation with AMH and INHB levels, and can also be used as indirect indices for evaluating ovarian reserve function. Cortisol, NE, and hs-CRP are important indices for evaluating the effect of patients receiving surgery, and these indices have important clinical significance for evaluating patients’ stress responses to surgery.[20]

In our study, intraoperative blood loss, operation time, and out of bed time in the experimental group were significantly less than those in the control group. Some studies[21] analyzed the clinical efficacy of laparoscopic surgery in treatment of endometriotic cysts. These studies showed that laparoscopic surgery for endometriotic cysts could effectively shorten the operation time and reduce intraoperative bleeding compared with laparotomy. The conclusions of this study are consistent with our results. Ovarian reserve function indices (FSH, LH, and AMH levels) in the experimental group were significantly lower than those in the control group. The maximum diameter of the ovary and the number of antral follicles were significantly less in the experimental group than in the control group. All of these results indicated that laparoscopic surgery had less trauma to the body than did laparotomy in treatment of ovarian cysts and could protect the patient’s ovarian reserve function. Our results on the various ovarian reserve function indices and ovarian conditions in the experimental group after surgery were better than those in the control group. Previous studies[22] have reported that surgical treatment of ovarian cysts can cause damage to follicles and granulosa cells in the ovary, and thus affect the level of reproductive hormones in patients. Reproductive hormones are an important index for evaluating ovarian reserve function. Therefore, we suspect that the reason that laparoscopic surgery had less effect on the body was because the damage to follicles and granulosa cells in the ovary was smaller than that of laparotomy. Therefore, ovarian function received a certain degree of protection with laparoscopic surgery. Previous studies[23] have investigated the effects of different hemostasis methods on ovarian reserve function during surgery. These studies showed that hemostasis of the surgical wound by electrocoagulation may cause damage to the primordial follicles and granulosa cells in the ovary. This causes corpus luteum cells to degenerate, resulting in abnormalities in hormone levels. Furthermore, the elevation in FSH levels was higher in patients using bipolar coagulation for hemostasis than in patients who were sutured to stop bleeding.[23] Therefore, we speculate that the reason for smaller changes in ovarian reserve function indices in the experimental group compared with the control group might be related to different methods of hemostasis.

Finally, we compared postoperative stress indices between the two groups. We found that changes in stress indices in the experimental group were significantly less than those in the control group. This result indicated that laparoscopic surgery had less damage and effect on the body than laparotomy, which could significantly reduce the patient’s stress response. However, there have been few studies on the stress response of laparoscopic surgery in patients with ovarian cysts.[24] Therefore, further studies on this issue are required. However, our findings indicated that laparoscopic surgery for ovarian cysts had less adverse effects than did laparotomy, and could better control the patient’s stress response and protect the patient’s ovarian reserve function. Many studies[25,26] have also reported the advantages of laparoscopic surgery for treating diseases. In a radial operation for carcinoma of the stomach,[27] use of laparoscopy results in less stress and immune responses to patients compared with traditional laparotomy. Previous studies[28] on the effect of laparoscopy in hysterectomy showed that patients treated with laparoscopic surgery had a shorter operative time, less bleeding, faster recovery, and fewer complications compared with traditional vaginal hysterectomy. These studies all support our conclusions.

In summary, compared with traditional laparotomy, laparoscopic ovarian cyst dissection may better protect ovarian reserve function, reduce the stress response, and promote postoperative recovery of patients. However, because of limited information on this issue and the small sample size of our study, further research is required to support our findings.