Impact of Laparoscopic Ovarian Cystectomy on Ovarian Reserve Assessed by Serum Anti-Mullerian Hormone in Benign Ovarian Cysts: A Prospective Observational Study

Ovarian reserve, indicative of follicle quantity and quality, is best measured by serum anti-Mullerian hormone (AMH) levels.[] AMH is a reliable marker of ovarian reserve, unaffected by menstrual cycle or hormonal treatments.[] Laparoscopic ovarian cystectomy (LOC) is a common treatment for benign ovarian cysts and endometriomas, but concerns exist about its impact on ovarian reserve due to potential damage to healthy ovarian tissue.[,] There is a lack of prospective evidence for the efficacy of laparoscopic cystectomy in fertility preservation. We correlated the AMH as a surrogate marker of ovarian reserve in patients undergoing laparoscopic cystectomy.

Patients Thirty women, aged 18–45 years, scheduled for LOC for cysts >4 cm were included. Exclusion criteria included suspicion of malignancy, prior adnexal surgery, recent hormone treatment, unfitness for surgery or pre-operative AMH <1 ng/mL. Study protocol Patients were screened based on the inclusion and exclusion criteria. Informed consent was obtained, and pre-operative AMH levels were recorded. Serum AMH was tested at AIIMS Raipur’s Department of Biochemistry using enzyme-linked immune sorbent assay (ELISA). Surgical details and post-operative AMH levels at 1 week and 1 month were documented. AMH levels were measured using ELISA with a detection limit of 0.017 ng/mL. Intra- and inter-assay coefficients of variation were 4.6% and 8.0%, respectively. The primary outcome was the change in AMH levels post-surgery, analysed in relation to cyst size, type, number, presence of adhesions, energy sources used and surgeon’s experience. The data were analysed using SPSS Statistics Version 2023. Descriptive statistics, t-tests, one-way ANOVA and Chi-squared tests were used. Correlations and multivariate regression analyses were performed.

The mean age in the study population was 31.27 ± 6.5 years, and the mean body mass index (BMI) was 21.57 ± 1.87 kg/cm2. Out of 30 patients, 25 had a single cyst and 5 with two cysts; 20 had benign ovarian cysts and 10 had endometriotic cysts. Adhesions were present in 13 patients. Nineteen patients had cyst sizes up to 10 cm and 11 patients had cyst sizes more than 10 cm. The mean size of the cyst was 8.89 ± 3.28 cm [Table 1]. The energy source was used in 53.3% of patients. We used a harmonic device for all cases. Thirteen surgeries were performed by a surgeon with experience of 4–6 years, 10 surgeries by a surgeon with experience of >6 years and 7 by a surgeon with experience of < 3 years. The mean pre-operative AMH was 2.46 ± 1.37 ng/mL and was significantly less in the age group of 35–45 years (1.68 ± 0.74 ng/ml) than 18–24 years age group (P = 0.036). There was no difference in mean pre-operative AMH with BMI and parity. The mean AMH in patients with infertility was 2.52 ± 0.9 ng/ml and with normal infertility was 2.41 ± 1.64 ng/ml with no statistically significant difference. The pre-operative AMH was less in endometrioma patients (1.99 ± 1.54 ng/ml) as compared to benign ovarian cysts (2.69 ± 1.54 ng/ml), but the difference was not statistically significant (P = 0.197). The mean duration of surgery was 106.47 ± 23.37 min. The duration of surgery was longer in the endometrioma group (118.4 ± 30.19 min) as compared to other benign ovarian cysts (100.5 ± 17.01 min), and the difference was statistically significant (P = 0.046). Duration of surgery was longer (116.23 ± 27.6 min) when adhesions were present as compared to when there were no adhesions (99 ± 16.8 min), and the difference was significant statistically (P = 0.043). There was a statistically significant fall in serum AMH at 1 week (P = 0.000) and 1 month (P = 0.000) postoperatively. The mean percentage fall of serum AMH on day 7 and 1 month was 57.50% and 37.46%, respectively. The AMH level increased significantly from 1 week to 1 month postoperatively (P = 0.000) and recovered to 34.74% of the pre-operative level [Table 2 and Figure 1]. We compared the role of age, cyst size, cyst type, multiplicity, presence of adhesions, use of energy sources and surgeon’s experience on the changes in AMH level after laparoscopic cystectomy [Table 3]. The fall in AMH was more in the multiple cyst group (1.95 ± 0.67 ng/ml) as compared to single cyst (1.29 ± 0.72 ng/ml) with marginal statistical significance (P = 0.067). As compared to endometriotic cysts (1.15 ± 0.52 ng/ml), the fall in AMH was more in benign ovarian cysts (1.52 ± 0.82 ng/ml) although the difference was not statistically significant (P = 0.200). The size of the cyst, presence of adhesions, use of energy source and surgeon’s experience had no relation with the fall of serum AMH level after surgery. A statistically significant negative correlation of increasing age with fall of serum AMH after laparoscopic cystectomy (−0.502) was seen. The size of cyst, duration of surgery in minutes and experience of the surgeon had a weak correlation with the fall of AMH which was not statistically significant. On performing multivariate regression analysis, age was a significant negative independent determinant for the fall in AMH on day 7 (−0.06).

Currently, LOC is considered the primary treatment of choice for benign ovarian tumours. The main benefit is thought to be a more complete excision of the tumour during the procedure. Nonetheless, reduction of residual ovarian function and increased risk of pre-mature ovarian failure induced by an excessive removal of healthy ovarian tissue remains an issue. The present study attempted to assess the reduction in AMH levels after LOC in cases of ovarian endometriomas and benign cysts of the ovary and to study the determinants of fall in AMH levels post-laparoscopic cystectomy. The mean age and BMI in our study population were 31.27 ± 6.5 and 21.57 ± 1.87 kg/cm2, respectively. The mean pre-operative serum AMH was 2.46 ± 1.37 ng/ml and was significantly less (1.68 ± 0.74) in the older age group of (35–45 years) and in endometrioma patients (1.99 ± 1.54 ng/ml) as compared to benign ovarian cysts (2.69 ± 1.54 ng/ml. Alborzi et al.[] also observed lower AMH level in women >38 years. Chen et al.[] and Uncu et al.[] observed lower AMH levels in the endometrioma group than other benign ovarian cysts. In the present study, AMH levels significantly decreased (P = 0.000) on the 7th day postoperatively compared with the pre-operative level and increased significantly (P = 0.000) at 1 month post-surgery. The mean percentage fall of serum AMH on day 7 was 57.50% and at 1 month was 37.46%. Chang et al.[] observed a decrease of serum AMH level at 1 week postoperatively (median = 0.67; range = 0.02–1.93; 95% confidence interval [CI]: 0.44–1.70 ng/mL). In the study of Alborzi et al. in 2014 on patients with endometrioma, serum AMH level decreased significantly from the baseline (3.86 ± 3.58 ng/mL) to 1 week (1.66 ± 1.92 ng/mL). Cho et al.[] in 2021 evaluated decrease in serum AMH level in patients with benign ovarian cysts and observed mild decrease in serum AMH level on day 7 (1.1 ± 2.98 ng/ml) and significant decrease at 6 months postoperatively (1.7 ± 4.34 ng/ml). The short-term fall in ovarian reserve can be explained by inadvertent removal or destruction of the healthy ovarian tissue adjacent to the pseudocapsule of the cyst containing functional follicles during the cystectomy. The reduction could be a consequence of damage to ovarian vasculature or an inflammation-mediated injury resulting in the loss of healthy ovarian follicles. It could be directly damaged from electrosurgical coagulation for haemostasis. Bipolar coagulation caused more damage to the ovarian reserve than suture haemostasis after ovarian cyst removal, as evidenced by a substantial post-operative drop in AMH as seen by Ding et al.[] In our study, the decreased serum AMH levels after surgery were recovered to 34.7% of pre-operative levels at 1 month, but the level did not reach the pre-operative serum AMH level. The AMH level increased significantly from 1 week to 3 months after operation (P < 0.001) in the study of Chen et al. Chang et al.[] al observed that the decreased serum AMH levels after surgery were increased at 1 month (1.14; 0.03–3.17; 95% CI: 0.79–2.36 ng/mL) and recovered to 65% of pre-operative levels at 3 months. Several mechanisms for the recovery of serum AMH levels have been postulated. It may be due to reperfusion of ovarian tissue and release of AMH produced from the remaining ovarian follicle pool after the ovarian vasculature has been re-established. The function of granulosa cells could be hyperactivated compensatory to ovarian damage in remaining follicles. Follicles can be rescued from atretic follicles. We observed the decrease in AMH was more in benign ovarian cysts (1.52 ± 0.82 ng/ml) as compared to endometriotic cysts (1.15 ± 0.52 ng/ml), although the difference was not statistically significant (P = 0.200). This finding is contrary to the observation by Chang et al. who found the fall of serum AMH level was more at 1 week post-operative in endometrioma compared with non-endometriotic cysts (33.9% vs. 69.2% of pre-operative AMH level, P = 0.028). This finding may be because the pre-operative size of the cyst was larger (9.48 ± 3.72 cm) in the benign ovarian cyst group compared with the endometrioma group (7.71 ± 1.74 cm) in our study and damage to normal ovarian tissue was more leading to more fall in ovarian reserve. The multiple cyst group showed more fall in AMH at 1 month (47.63%) as compared to single cyst (35.42%) with less recovery rate at the end of the month. Chang et al. and Kwon et al.[] also observed that the patients who underwent bilateral cystectomy had significantly decreased serum AMH levels compared with those who underwent unilateral cystectomy during 3 months post-operative. This shows that the more the number of cysts, the more inadvertent injury to normal tissue and more fall in amh at one month. The duration of surgery was significantly longer in the endometrioma group (118.4 ± 30.19 min) as compared to other benign ovarian cysts and in the presence of adhesions. Kwon et al. in their study found increased duration of surgery in the endometrioma group as compared to benign ovarian cysts group. In our study, we tried to find out the correlation of intra-operative determinants like the presence or absence of adhesions, use of energy sources, technique of cystectomy and the experience of the surgeon with the fall in serum AMH. By applying Pearson’s analysis, we observed a weak positive correlation between size of the cyst, duration of surgery in minutes and experience of the surgeon with the fall of AMH which was not statistically significant. In addition to increasing surgical skills, one should also follow the principles of microsurgery to reduce damage to normal tissue. Chen et al. observed the rate of serum AMH level decline for bilateral cysts was larger than for unilateral cysts in the endometrioma group but not in the other benign ovarian cyst group. The pre-operative AMH level was low in older women with a statistically significant negative correlation of increasing age with fall of serum AMH after laparoscopic cystectomy in our study. Similar result was seen by Chen et al. in their study. Therefore, this result implied that it was necessary to measure the pre-operative ovarian reserve prior to cystectomy in older patients. If the pre-operative serum AMH is too low, then we should consider evaluating the risk of post-operative ovarian failure. There was no statistically significant positive or negative correlation of age, BMI, size of cysts, duration of surgery and surgeon’s experience with the post-operative day 30 increase of serum AMH. The intraoperative determinants such as the presence of adhesions and surgeon’s experience were not correlated with fall of AMH postoperatively in the previously done studies. Although the statistical power of our study was diminished somewhat by the small number of study subjects and short follow-up intervals, our results are consistent with other published results about the cystectomy effect on ovarian reserve. Considering the follicular life span, a further assessment at least 6 months would have been more informative.

From the present study, we conclude that LOC is associated with a decreased ovarian reserve, measured by serum AMH levels, in the immediate post-operative period. The decreased reserve was recovered to some extent at 1 month post-operative. The measurement of AMH level after LOC could be helpful in deciding when to start ovarian stimulation after the operation, although further long follow-up study is needed before it can be routinely used. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

We would like to express our heartfelt gratitude to all individuals of AIIMS Raipur whose invaluable contributions made this research possible. We sincerely appreciate the NMO Journal for providing a platform to disseminate our findings. We extend our gratitude to Dr. Vinita Singh, Dr. Chandrashekhar Shrivastava and Dr. Sarita Rajhbhar for their expertise, collaboration and shared passion for conducting this study. We are immensely grateful to our colleagues and mentors, whose guidance, wisdom and valuable insights steered us in the right direction throughout the research process. We extend our sincere appreciation to the participants of this study, whose voluntary involvement and cooperation made it possible to collect the necessary data. We would also like to acknowledge the support and resources provided by AIIMS, Raipur. Their infrastructure, access to databases and research facilities played a critical role in facilitating data collection, analysis and interpretation.

1 Fanchin R, Schonäuer LM, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod 2003;18:323–72 Seifer DB, Maclaughlin DT. Mullerian inhibiting substance is an ovarian growth factor of emerging clinical significance. Fertil Steril 2007;88:539–463 Alborzi S, Momtahan M, Parsanezhad ME, Dehbashi S, Zolghadri J, Alborzi S. A prospective, randomized study comparing laparoscopic ovarian cystectomy versus fenestration and coagulation in patients with endometriomas. Fertil Steril 2004;82:1633–74 Beretta P, Franchi M, Ghezzi F, Busacca M, Zupi E, Bolis P. Randomized clinical trial of two laparoscopic treatments of endometriomas: Cystectomy versus drainage and coagulation. Fertil Steril 1998;70:1176–805 Alborzi S, Keramati P, Younesi M, Samsami A, Dadras N. The impact of laparoscopic cystectomy on ovarian reserve in patients with unilateral and bilateral endometriomas. Fertil Steril 2014;101:427–346 Chen Y, Pei H, Chang Y, Chen M, Wang H, Xie H, et al. The impact of endometrioma and laparoscopic cystectomy on ovarian reserve and the exploration of related factors assessed by serum anti-Mullerian hormone: A prospective cohort study. J Ovarian Res 2014;7:1087 Uncu G, Kasapoglu I, Ozerkan K, Seyhan A, Oral Yilmaztepe A, Ata B. Prospective assessment of the impact of endometriomas and their removal on ovarian reserve and determinants of the rate of decline in ovarian reserve. Hum Reprod 2013;28:2140–58 Chang HJ, Han SH, Lee JR, Jee BC, Lee BI, Suh CS, et al. Impact of laparoscopic cystectomy on ovarian reserve: Serial changes of serum anti-Müllerian hormone levels. Fertil Steril 2010;94:343–99 Cho HY, Park ST, Park SH, Kyung MS. Anti-Mullerian hormone changes following laparoscopic ovarian cystectomy: A prospective comparative study. Int J Womens Health 2021;13:691–810 Ding W, Li M, Teng Y. The impact on ovarian reserve of haemostasis by bipolar coagulation versus suture following surgical stripping of ovarian endometrioma: A meta-analysis. Reprod Biomed Online 2015;30:635–4211 Kwon SK, Kim SH, Yun SC, Kim DY, Chae HD, Kim CH, et al. Decline of serum antimüllerian hormone levels after laparoscopic ovarian cystectomy in endometrioma and other benign cysts: A prospective cohort study. Fertil Steril 2014;101:435–41