Comparison of ovarian preservation versus oophorectomy on fertility outcomes in patients with endometriosis post-laparoscopic surgery: A prospective study

Abstract

BACKGROUND

Endometriosis is a chronic inflammatory condition affecting a significant proportion of women of reproductive age. Although laparoscopic surgery is commonly the preferred treatment, the decision to preserve or remove the ovaries remains controversial. Previous studies have yielded inconsistent results regarding the impact of ovarian preservation vs oophorectomy on fertility outcomes and disease recurrence. This prospective study aimed to address this knowledge gap by comparing the effects of these surgical approaches on spontaneous pregnancy rates, time to pregnancy, recurrence rates, and postoperative pain in patients with endometriosis.

AIM

To compare the reproductive outcomes and recurrence rates between ovarian preservation and oophorectomy in women undergoing laparoscopic surgery for endometriosis.

METHODS

This study was conducted at a tertiary care hospital between January 2019 and December 2023. A total of 312 women aged 18 to 40 years, diagnosed with endometriosis and undergoing laparoscopic surgery, were included. The patients were categorized into the ovarian preservation group (n = 204) and the oophorectomy group (n = 108). The primary outcome measure was the achievement of spontaneous pregnancy within 24 months post-surgery. Secondary outcomes included time to spontaneous pregnancy, recurrence rates, and postoperative pain scores.

RESULTS

The ovarian preservation group exhibited a significantly higher spontaneous pregnancy rate than that in the oophorectomy group (43.6% vs 28.7%, P = 0.006). Moreover, the median time to spontaneous pregnancy was shorter in the ovarian preservation group (8.2 months vs 11.4 months, P = 0.018). Nonetheless, endometriosis recurrence was more prevalent in the ovarian preservation group (22.1% vs 11.1%, P = 0.014). The postoperative pain scores demonstrated similar improvements in both groups, with no significant differences observed. Subgroup analyses indicated that the benefit of ovarian preservation on spontaneous pregnancy rates was more evident among younger women (≤ 35 years) and those with advanced-stage endometriosis.

CONCLUSION

Ovarian preservation is associated with a high spontaneous pregnancy rate and a short time to pregnancy. However, because of the increased risk of recurrence, the decision should be based on age, fertility aspirations, and disease severity.

Key Words: Endometriosis; Ovarian; Pregnancy; Oophorectomy; Laparoscopic; Spontaneous pregnancy

Core Tip: Preserving ovaries during laparoscopic surgery for endometriosis enhances spontaneous pregnancy rates and reduces time to conception. However, increased risk of disease recurrence necessitates individualized decision-making based on patient age, fertility goals, and disease severity.

INTRODUCTION

Endometriosis, characterized by the presence of endometrial-like tissue outside the uterine cavity, is a chronic inflammatory condition affecting approximately 10%–15% of women of reproductive age[1,2]. Endometriosis is a primary cause of pelvic pain, dysmenorrhea, dyspareunia, and infertility, significantly impacting the quality of life of those affected[3,4]. Despite extensive research, the exact etiology of endometriosis remains elusive, with proposed theories including retrograde menstruation, coelomic metaplasia, and immunological factors[5].

The management of endometriosis necessitates a multidisciplinary approach integrating both medical and surgical interventions. Medical therapy, which includes hormonal treatments such as combined oral contraceptives, progestins, and gonadotropin-releasing hormone (GnRH) agonists, aims to alleviate symptoms and potentially inhibit the growth of endometriotic lesions[6]. However, these treatments are not curative and may involve significant side effects, particularly with long-term use[7].

Surgical intervention is often recommended, particularly in cases involving ovarian endometriomas, deep infiltrating endometriosis, or when medical therapy fails to provide adequate symptom relief[4,8]. Laparoscopic surgery is the gold standard for the treatment of endometriosis, offering numerous advantages over traditional open surgery, including shorter recovery times, reduced postoperative pain, and improved cosmetic outcomes[9].

During laparoscopic surgery for endometriosis, gynecologists encounter the dilemma of preserving or removing the ovaries (oophorectomy). Ovarian preservation provides potential benefits, including fertility preservation and maintenance of hormonal balance, whereas oophorectomy may decrease the risk of recurrence but entails compromising ovarian function[5,10].

Preserving the ovaries during endometriosis surgery has been advocated because of its potential benefits in maintaining fertility and hormonal function. This approach may be particularly advantageous for women who desire future pregnancy or aim to avoid the adverse effects associated with premature menopause, such as vasomotor symptoms, osteoporosis, and cardiovascular disease[11,12].

Several studies have reported improved fertility rates following ovarian preservation during endometriosis surgery[13,14]. However, the potential risk of endometriosis recurrence after ovarian preservation remains a concern, as residual ovarian tissue may contribute to the development of new endometriotic lesions[15,16].

The rationale for performing oophorectomy during endometriosis surgery is primarily based on the potential reduction in the risk of recurrence. By removing the ovaries, which are common sites for endometriotic lesions, the source of estrogen production is eliminated, potentially inhibiting the growth and progression of residual endometriotic tissue[17].

Despite the potential benefit of reduced recurrence, oophorectomy carries significant consequences, particularly in women of reproductive age. The removal of one or both ovaries disrupts ovarian function, leading to hormonal imbalances and potential adverse effects such as vasomotor symptoms, decreased libido, and an increased risk of osteoporosis and cardiovascular disease[18,19]. Additionally, oophorectomy eliminates the possibility of future natural conception, necessitating the use of assisted reproductive technologies for those desiring children.

The impact of ovarian preservation vs oophorectomy on postoperative fertility outcomes in women with endometriosis is a subject of ongoing debate. Several studies have investigated this topic; however, the results have been inconsistent[20,21].

A few studies reported higher spontaneous pregnancy rates after ovarian preservation[13,14], while others found no significant differences in fertility outcomes between the two approaches[22,23]. These conflicting findings highlight the complexity of the issue and the potential influence of various factors, such as age, severity of endometriosis, extent of surgery, and the presence of other infertility factors.

Given the inconsistent findings and significant implications of the surgical approach on fertility and overall health, well-designed prospective studies are needed to provide further insights into the impact of ovarian preservation vs oophorectomy on postoperative fertility outcomes in patients with endometriosis. This prospective cohort study aimed to provide valuable evidence to guide clinical decision-making and counseling for women with endometriosis. Through the investigation of a large patient cohort and assessing diverse fertility-related outcomes, including spontaneous pregnancy rates, time to spontaneous pregnancy, and recurrence rates, this study has the potential to illuminate the optimal surgical approach for various patient populations.

MATERIALS AND METHODS

Study design and participants

This prospective cohort study was conducted at a tertiary care hospital between January 2019 and December 2023. Women aged 18 to 40 years, diagnosed with endometriosis according to the revised American Society for Reproductive Medicine (ASRM) stages I–IV[24], and undergoing laparoscopic surgery were eligible for inclusion. Exclusion criteria included previous ovarian surgery, the presence of other causes of infertility, such as tubal factor or male factor, concurrent malignancies, and the use of hormonal medications within three months before surgery.

A total of 312 patients meeting the eligibility criteria were enrolled in the study after providing written informed consent. The study protocol was approved by the institutional review board of the participating center.

Surgical procedure and group allocation

All laparoscopic surgeries were performed by an experienced team of gynecological surgeons following standardized procedures. Patients were assigned to one of two groups based on the surgical approach: The ovarian preservation group or the oophorectomy group.

In the ovarian preservation group (n = 204), ovarian endometriomas were managed through cystectomy or drainage, while other endometriotic lesions were surgically excised or ablated using electrosurgical techniques or plasma energy. Ovaries were preserved, and oophorectomy was performed based on intraoperative findings of severe ovarian involvement or other complications. In the oophorectomy group (n = 108), patients underwent either unilateral or bilateral oophorectomy, depending on the extent and severity of ovarian involvement. Similar to the ovarian preservation group, other endometriotic lesions were managed through excision or ablation.

The determination regarding ovarian preservation or oophorectomy was reached after a thorough evaluation of the patient’s age, desire for future fertility, severity of endometriosis (based on ASRM staging), and intraoperative findings. Generally, ovarian preservation was favored for women under 35 years of age with a desire for future fertility, unless severe ovarian involvement or complications necessitated oophorectomy. Conversely, oophorectomy was considered more readily for women over 35 years of age or those without fertility desires, particularly in cases of severe ovarian endometriosis or recurrent endometriomas.

Surgical staging and documentation

During the laparoscopic procedure, a comprehensive examination of the pelvic and abdominal cavities was performed. The updated ASRM scoring system[24] was used to determine the extent and severity of endometriosis. This system assigns scores based on the location, size, and depth of endometriotic lesions, and the presence and severity of adhesions.

Detailed surgical records were maintained, encompassing descriptions of the endometriotic lesions, surgical procedures performed (such as cystectomy, excision, and ablation), and any intraoperative complications or additional procedures (such as oophorectomy or adhesiolysis).

Outcome measures

The primary outcome of the study centered on the attainment of spontaneous pregnancy within 24 months following surgery. Secondary outcomes encompassed time to spontaneous pregnancy (defined as the duration between surgery and confirmation of pregnancy), endometriosis recurrence rates (assessed through clinical symptoms and imaging findings), evaluation of postoperative pain scores [utilizing a Visual Analog Scale (VAS) at 3, 6, 12, and 24 months post-surgery], and incidence of surgical complications, including both intraoperative and postoperative occurrences.

Follow-up and data collection

Patients underwent regular follow-up appointments at intervals of 3, 6, 12, and 24 months post-surgery. Relevant information was collected during each follow-up visit, encompassing menstrual history and pregnancy status (validated by a positive serum human chorionic gonadotropin test or ultrasound examination), assessment of endometriosis symptom recurrence (including pelvic pain, dysmenorrhea, and dyspareunia), documentation of pain levels using a VAS ranging from 0 (no pain) to 10 (worst imaginable pain), and identification and documentation of any adverse events or complications attributable to surgery or treatment.

Transvaginal ultrasound or magnetic resonance imaging was conducted as necessary to assess for the recurrence of endometriotic lesions or endometriomas. Patients exhibiting signs of recurrence underwent diagnostic laparoscopy for confirmation and subsequent management.

Sample size calculation

The sample size was calculated based on the primary outcome of spontaneous pregnancy rates. Employing a two-sided alpha of 0.05% and 80% power and assuming a spontaneous pregnancy rate of 45% in the ovarian preservation group and 30% in the oophorectomy group (based on previous studies)[25,26], a minimum sample size of 286 patients (143 per group) was determined to be necessary to detect a statistically significant difference. Accounting for a potential dropout rate of 10%, the target enrollment was established at 312 patients.

Statistical analysis

The baseline characteristics of the two groups were summarized using descriptive statistics. Continuous variables were compared using the Student's t-test or Mann–Whitney U test, as deemed appropriate, while categorical variables were compared using either the χ² test or Fisher's exact test. The primary outcome, spontaneous pregnancy rate, was analyzed using the χ² test. Kaplan–Meier curves and log-rank tests were used to compare the time to spontaneous pregnancy between the two groups. Additionally, Cox proportional hazards regression analysis was performed to identify potential predictors of spontaneous pregnancy, with adjustments made for confounding variables such as age, body mass index, ASRM stage, and prior pregnancies. Recurrence rates and postoperative pain scores were compared between the two groups using appropriate statistical tests (χ² or Fisher's exact test for recurrence rates and repeated measures analysis of variance or generalized estimating equations for pain scores). Subgroup analyses were conducted to evaluate the impact of factors such as age, ASRM stage, and surgical technique on the study outcomes. Surgical complications were summarized using descriptive statistics and compared between the two groups using either the χ² test or Fisher's exact test. A P value of < 0.05 was considered statistically significant. All statistical analyses were performed using dedicated software (SPSS, R, or SAS).

RESULTS

Baseline characteristics

A total of 312 patients were included in the final analysis, comprising 204 in the ovarian preservation group and 108 in the oophorectomy group. The baseline characteristics of both groups were well-matched and demonstrated no significant differences (Table 1). The mean age was 32.4 ± 4.8 years in the ovarian preservation group and 34.1 ± 5.2 years in the oophorectomy group. The majority of the patients in both groups were nulliparous, accounting for 67.2% and 71.3%, respectively. Moreover, the distribution of the ASRM endometriosis stages was similar between the two groups, with a predominant proportion of patients exhibiting stage III or IV disease.

Table 1 Baseline characteristics, n (%).

Characteristic	Ovarian preservation group (n = 204)	Oophorectomy group (n = 108)	P value
Age (years), mean ± SD	32.4 ± 4.8	34.1 ± 5.2	0.11
BMI (kg/m2), mean ± SD	24.6 ± 3.9	25.1 ± 4.2	0.28
Nulliparous	137 (67.2)	77 (71.3)	0.45
ASRM stage
I	22 (10.8)	9 (8.3)	0.51
II	38 (18.6)	17 (15.7)	0.54
III	81 (39.7)	46 (42.6)	0.63
IV	63 (30.9)	36 (33.3)	0.67

ASRM: American Society for Reproductive Medicine; BMI: Body mass index.

Primary outcome: Spontaneous pregnancy rates

The spontaneous pregnancy rate within 24 months post-surgery differed significantly between the ovarian preservation and oophorectomy groups (43.6% vs 28.7%, P = 0.006). The Kaplan–Meier analysis underscored this discrepancy, revealing a consistently elevated cumulative probability of spontaneous pregnancy in the ovarian preservation group across the entire 24-month follow-up period (log-rank test, P = 0.002).

Secondary outcomes

Time for spontaneous pregnancy: Among patients who attained spontaneous pregnancy, the median time to pregnancy was notably shorter in the ovarian preservation group than that in the oophorectomy group (8.2 months vs 11.4 months, P = 0.018).

Endometriosis recurrence

The rate of endometriosis recurrence, defined as the reappearance of endometriotic lesions or symptoms necessitating surgical or medical intervention, exhibited a higher prevalence in the ovarian preservation group compared to that in the oophorectomy group (22.1% vs 11.1%, P = 0.014). The median time to recurrence in the ovarian preservation group and the oophorectomy group was 18.2 months and 20.4 months, respectively.

Postoperative pain scores

Evaluation of postoperative pain scores using the VAS revealed a significant decrease in both groups over time (both P <0.001). However, no significant difference in pain scores was observed between the two groups at any time point during the 24-month follow-up period (P > 0.05) (Table 2).

Table 2 Postoperative pain scores (visual analog scale).

Time point	Ovarian preservation group (n = 204)	Oophorectomy group (n = 108)	P value
3 months	2.8 ± 1.6	2.6 ± 1.8	0.31
6 months	2.1 ± 1.4	1.9 ± 1.6	0.27
12 months	1.5 ± 1.2	1.3 ± 1.1	0.19
24 months	1.1 ± 0.9	0.9 ± 0.8	0.07

Surgical complications

The overall incidence of intraoperative and postoperative complications did not present significant differences between the two groups (12.3% in the ovarian preservation group vs 14.8% in the oophorectomy group, P = 0.51). The predominant complications encompassed bleeding, infection, and bladder or bowel injury, with comparable frequencies observed in both groups (Table 3).

Table 3 Surgical complications, n (%).

Complication	Ovarian preservation group (n = 204)	Oophorectomy group (n = 108)	P value
Any complication	25 (12.3)	16 (14.8)	0.51
Bleeding	8 (3.9)	6 (5.6)	0.51
Infection	6 (2.9)	3 (2.8)	0.93
Bladder/bowel injury	4 (2.0)	3 (2.8)	0.63
Others	7 (3.4)	4 (3.7)	0.9

Subgroup analyses

Subgroup analyses were performed to evaluate the impact of age, ASRM stage, and surgical technique on the study outcomes. In patients aged ≤ 35 years, the spontaneous pregnancy rate was significantly higher in the ovarian preservation group compared to that in the oophorectomy group (50.8% vs 31.6%, P = 0.002). Conversely, in patients aged > 35 years, no significant difference in spontaneous pregnancy rates was observed between the two groups (26.7% vs 22.2%, P = 0.61) (Table 4).

Table 4 Spontaneous pregnancy rates by age subgroup.

Age subgroup	Ovarian preservation group	Oophorectomy group	P value
≤ 35 years	50.8% (74/146)	31.6% (24/76)	0.002
35 years	26.7% (15/58)	22.2% (7/32)	0.61

Stratification by the ASRM stage demonstrated significantly higher spontaneous pregnancy rates in patients with stage III (46.9% vs 30.2%, P = 0.017) and stage IV (39.5% vs 24.1%, P = 0.038) endometriosis in the ovarian preservation group, whereas no significant difference was discerned in those with stage I or II disease (Table 5).

Table 5 Spontaneous pregnancy rates by American Society for Reproductive Medicine stage.

ASRM stage	Ovarian preservation group	Oophorectomy group	P value
I/II	38.3% (23/60)	34.6% (9/26)	0.73
III	46.9% (38/81)	30.2% (14/46)	0.017
IV	39.5% (28/63)	24.1% (8/36)	0.038

ASRM: American Society for Reproductive Medicine.

The surgical technique (cystectomy vs drainage for endometriomas) did not significantly affect the spontaneous pregnancy rates or recurrence rates in the ovarian preservation group (Table 6).

Table 6 Outcomes by surgical technique (ovarian preservation group).

Outcome	Cystectomy (n = 138)	Drainage (n = 66)	P value
Spontaneous pregnancy rate	44.9% (62/138)	40.9% (27/66)	0.58
Recurrence rate	20.3% (28/138)	25.8% (17/66)	0.37

DISCUSSION

This prospective cohort study offers significant insights into the complex decision-making process involved in the surgical management of endometriosis, particularly concerning the delicate balance between preserving fertility and minimizing disease recurrence. The key findings highlight the potential reproductive advantages associated with ovarian preservation, despite emphasizing the necessity for meticulous patient selection and counseling regarding the attendant risks.

The significantly higher spontaneous pregnancy rate observed in the ovarian preservation group (43.6% vs 28.7%) is consistent with previous studies[27], reinforcing the critical role of preserving the ovarian reserve for optimizing fertility outcomes. Oophorectomy, particularly in younger women, carries the risk of precipitating a premature decline in ovarian function, thereby compromising future fertility potential[28]. Moreover, the shorter time to spontaneous pregnancy observed in the ovarian preservation group (median 8.2 months vs 11.4 months) further underscores the fertility advantages associated with this approach. Facilitating prompt conception post-surgery may reduce the risk of endometriosis recurrence and diminish the need for additional interventions.

Subgroup analyses revealed a more pronounced benefit of ovarian preservation on spontaneous pregnancy rates among women aged ≤ 35 years and those with advanced-stage endometriosis (stages III and IV). This observation aligns with that of previous research[29], which emphasized the importance of factoring age and disease severity when determining the optimal surgical approach.

For younger women harboring a fervent desire for future fertility, ovarian preservation should be strongly advocated, even in the presence of advanced endometriosis. Conversely, in older women or those without fertility desires, the potential risks associated with ovarian preservation, such as disease recurrence and the need for additional interventions, may outweigh the fertility benefits, rendering oophorectomy a more appropriate option.

The elevated rate of endometriosis recurrence observed in the ovarian preservation group (22.1% vs 11.1%) underscores a well-established trade-off associated with this approach[30]. Residual endometriotic tissue or microscopic lesions may contribute to the development of recurrent disease. Conversely, while oophorectomy reduces the risk of recurrence by eliminating the ovarian source of hormonal stimulation, it is accompanied by compromised fertility and potential long-term adverse consequences, including heightened risks of cardiovascular disease and osteoporosis[31].

The decision to pursue ovarian preservation necessitates careful consideration of various factors, including the patient's age, fertility desires, and the severity and extent of endometriosis. In younger women harboring a fervent desire for future fertility, the potential benefits of ovarian preservation may outweigh the risk of recurrence, particularly if coupled with diligent follow-up and prompt management of recurrent disease. In contrast, for older women or those lacking fertility aspirations, the reduced risk of recurrence associated with oophorectomy may constitute a more appropriate option.

In the current study, the choice of surgical technique (cystectomy vs drainage) for managing ovarian endometriomas did not significantly impact the rates of spontaneous pregnancy or recurrence in the ovarian preservation group. This finding aligns with certain previous studies[32] but contradicts others[33], indicating that the optimal surgical approach for endometriomas remains a topic of ongoing debate.

The study did not address the potential impact of postoperative hormonal therapy or adjuvant medical treatments on recurrence rates and reproductive outcomes. Several studies have investigated the role of adjuvant therapies, such as GnRH agonists, combined oral contraceptives, or aromatase inhibitors, in reducing the risk of endometriosis recurrence post-surgery[34]. A systematic review by Küpker et al[34] suggested that GnRH antagonists may be effective in treating endometriosis-related symptoms and reducing recurrence rates. However, the long-term effects of these treatments on fertility outcomes remain unclear. Additionally, the use of postoperative oral contraceptive pills has been associated with a reduced risk of anatomical relapse and symptom recurrence in a few studies[26], but the evidence is inconclusive. Future research should focus on elucidating the role of adjuvant therapies in optimizing surgical outcomes and preserving the fertility of patients with endometriosis.

Future research should focus on optimizing surgical techniques and adjuvant therapies to improve reproductive outcomes while minimizing the risk of disease recurrence. Personalized approaches, grounded in individual patient characteristics, disease severity, and fertility desires, may be warranted.

This study observed that postoperative pain scores improved significantly over time in both the ovarian preservation and oophorectomy groups, with no significant differences between the two cohorts. This finding suggests that both surgical modalities effectively alleviate endometriosis-associated pelvic pain, at least within the short-term context of the 24-month follow-up period.

However, it is important to note that the study did not evaluate the long-term sustainability of pain relief or the potential influence of disease recurrence on pain outcomes. Previous studies have suggested that endometriosis recurrence may lead to a resurgence of pelvic pain and other associated symptoms[35]. Therefore, long-term follow-up and assessment of pain outcomes in the context of recurrence rates would be valuable in determining the optimal surgical approach for pain management.

The strengths of this study include its prospective design, standardized surgical procedures, and comprehensive follow-up assessments. The inclusion of a comparator group (oophorectomy) facilitated a direct comparison of reproductive outcomes and recurrence rates between the two surgical modalities.

However, several limitations merit acknowledgment. The relatively brief follow-up period of 24 months may potentially underestimate the long-term recurrence rates and fertility outcomes. Given the chronic nature of endometriosis, the risk of recurrence and associated complications may escalate over time[36,37]. Hence, longer follow-up periods would provide more comprehensive insights into the long-term implications of ovarian preservation vs oophorectomy.

Additionally, the study did not address the potential influence of postoperative hormonal therapy or adjuvant medical treatments, which may exert an impact on recurrence rates and reproductive outcomes. Future studies integrating these variables would provide a more holistic evaluation of the overall management strategies for endometriosis.

Furthermore, the study did not consider the potential impact of the surgical approach on ovarian reserve markers, such as anti-Müllerian hormone levels or antral follicle counts. These markers hold significant value in offering insights into residual ovarian function and fertility potential following surgery[38]. Incorporating ovarian reserve assessments into future studies could contribute to refining surgical decision-making processes and facilitating informed counseling for patients regarding their fertility prospects.

CONCLUSION

In conclusion, this prospective cohort study highlights the complex trade-offs inherent in the surgical management of endometriosis, particularly when considering fertility preservation against the risk of disease recurrence. Ovarian preservation during laparoscopic surgery was associated with superior spontaneous pregnancy rates and an expedited time to pregnancy compared to that in oophorectomy. However, this advantage is accompanied by an increased risk of endometriosis recurrence. The decision to pursue ovarian preservation should be individualized, considering variables such as age, fertility desires, and disease severity. In younger women with a strong desire for future fertility, particularly those with advanced-stage endometriosis, ovarian preservation may be the preferred approach, coupled with vigilant follow-up and timely management of recurrent disease. Conversely, in older women or those lacking fertility desires, the diminished recurrence risk associated with oophorectomy may outweigh the potential fertility benefits.