Reproductive and Developmental Medicine

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 3  |  Issue : 3  |  Page : 148--152

Fertility and sexual function after loop electrosurgical excision procedure in patients with high-grade squamous intraepithelial lesion


Meng Yu, Jing-Xin Ding, Ke-Qin Hua 
 Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China

Correspondence Address:
Ke-Qin Hua
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011
China

Abstract

Objective: Loop electrosurgical excision procedure (LEEP) is the first choice for patients with high-grade squamous intraepithelial lesion (HSIL). This study aimed to investigate postoperative fertility and sexual function in patients with HSIL after LEEP. Methods: This cohort study included patients with HSIL enrolled at 11 obstetrics and gynecology hospitals between January 1, 2013, and December 31, 2015. The patients were treated with LEEP only. Ultimately, 760 patients meet our inclusion and exclusion criteria. Our research included two parts: The effect of LEEP on postoperative fertility and the effect of LEEP on postoperative sexual function. In the two different parts of the research, we chose different case series according to their follow up information. Results: In the LEEP group, 125 patients had successful deliveries and 27 were preterm (21.6%). The risk of preterm birth was significantly higher in the case group (relative risk [RR]: 2.634; 95% confidence interval [CI]: 1.689–4.108). As the cone depth and volume increased, the risk of preterm increased. In this study, the raw relative risk of cesarean section (CS) was increased in the LEEP group, however the constituent ratio of the indications in the LEEP group was not significantly different from that of the control group. With increased cone depth and volume, pain during postoperative sexual intercourse gradually increased. Conclusions: LEEP increases the risk of preterm birth. The risk increases as the cone depth and volume increases. LEEP could lead to pain during sexual intercourse.



How to cite this article:
Yu M, Ding JX, Hua KQ. Fertility and sexual function after loop electrosurgical excision procedure in patients with high-grade squamous intraepithelial lesion.Reprod Dev Med 2019;3:148-152


How to cite this URL:
Yu M, Ding JX, Hua KQ. Fertility and sexual function after loop electrosurgical excision procedure in patients with high-grade squamous intraepithelial lesion. Reprod Dev Med [serial online] 2019 [cited 2020 Jul 4 ];3:148-152
Available from: http://www.repdevmed.org/text.asp?2019/3/3/148/268164


Full Text



 Introduction



The widespread use of screening has enabled early detection of cervical cancers and precancerous lesions. The traditional treatment for early cervical cancer and cervical precancerous lesions is hysterectomy. This treatment deprives women of fertility and may be considered excessive.[1] High-grade squamous intraepithelial lesion (HSIL) refers to a type of cervical intraepithelial neoplasia (CIN), including CIN II and CIN III. HSIL has a tendency to develop malignant transformation and must be treated appropriately to prevent progression. Conization is regarded as the most accurate diagnostic approach, and can also be used to treat HSIL. This treatment also allows the preservation of fertility.

Conization includes cold-knife conization (CKC) and a loop electrosurgical excision procedure (LEEP). Many studies have demonstrated that LEEP is superior to CKC, with the advantages of being easy to learn and having a short operative time, less intraoperative bleeding, rapid recovery, and minimal influence on fertility.[2],[3] LEEP is the first choice for patients with HSIL;[4] however, LEEP still can cause some damage to the cervix and may affect postoperative fertility. It has been reported that, when the excised tissue depth is greater than 15 mm, the risk of preterm birth is significantly increased.[5] The main concerns about postoperative fertility problems associated with LEEP include the following: whether LEEP will affect postoperative fertility, and whether key features of LEEP are associated with these adverse effects.

Studies on LEEP have mainly focused on the impact on postoperative fertility rather than postoperative sexual function. Some studies reported that LEEP had no obvious influence on sexual function.[6] However, others reported different results in postoperative sexual function, depending on the depth of cervical excision using LEEP.[7] Some reports even demonstrated that patients who underwent LEEP were more likely to have better postoperative sexual function than those who only underwent colposcopy.[8] The effects of LEEP on sexual function have rarely been reported for a large sample size. This multi-center study explored the effects of LEEP on postoperative fertility and sexual function.

 Methods



Subjects

We included women under 35 years old from 11 obstetrics and gynecology hospitals who were diagnosed with HSIL between January 1, 2013, and December 31, 2015. These patients were all diagnosed with HSIL by cytology and colposcopic biopsy before LEEP.

Patients were excluded from the study if their status after LEEP could not be determined, if they were diagnosed with infiltrative cervical cancer at any time, or if they chose to undergo hysterectomy for any reason. The basic information of the patients was extracted from medical records. The depth and volume of the cervix excised with LEEP was obtained from pathology reports. Follow-up was conducted by telephone and email. On follow-up, questions about the postoperative fertility of the patient, and a Female Sexual Function Index-19 (FSFI-19) questionnaire was completed. Standard case report form was used to collect information in all of the 11 Obstetrics and Gynecology Hospitals. Ultimately, 760 patients meet our inclusion and exclusion criteria. Our research included two parts: the effect of LEEP on postoperative fertility and the effect of LEEP on postoperative sexual function. In the two different parts of the research, we chose different case series according to their follow up information. One hundred and twenty-five cases had live births after LEEP. All were singleton births. We included only these 125 patients in the final analysis of the effects of LEEP on fertility. Simultaneously, we chose 500 women as control by using a hospital stratification and delivery time matching (a ratio of 1:2) randomly sampling method from 43,836 who recorded singleton births at the 11 Obstetrics and Gynecology Hospitals. The women in the control group were all with no cervical lesions and no history of cervical treatment. We compared their fertility outcomes. A total of 561 patients completed the FSFI-19 questionnaire. The FSFI-19 questionnaire involves 6 dimensions about female sexual function including desire, sexual arousal, lubricity, orgasm, satisfaction, and pain. We can obtain scores for each dimension and a total score for the overall sexual function. This scale is the most commonly used scale to quantize and compare the female sexual function. Only the 561 patients with completed FSFI-19 questionnaire were included in the final analysis of the effects of LEEP on sexual function [Supplementary Figure 1].[INLINE:1]

Statistical methods

All statistical analyses were conducted using SPSS version 22.0 (SPSS Inc., Chicago, IL, USA) software, and the level of significance was set at P < 0.05. The Wilcoxon test was used to analyze the data of the two groups with a nonnormal distribution. The Chi-squared test was used to analyze the categorical data. The Kruskal–Wallis h-test was used to analyze the data from three groups.

 Results



Effects of loop electrosurgical excision procedure on fertility

The average age of the 125 patients was 27.97 ± 3.47 years, the average preoperative gravidity was 1.50 ± 1.23, and the average preoperative parity was 0.50 ± 0.66. In addition, all infants were singletons. Controls included 500 randomly selected cases without cervical lesions. No significant differences in baseline information were observed between the two groups [Table 1]. The mainly points we focus on fertility was whether the delivery was preterm and whether the delivery is through vagina or by caesarean section. And the main factors about LEEP were cone depth and cone volume. Thus, in our study, we demonstrated how the two factors affected the fertility.{Table 1}

In the LEEP group, 27 (21.60%) of 125 patients experienced preterm birth, whereas only 41 (8.20%) experienced preterm birth in the control group. Compared with the control group, the rate of preterm birth was obviously increased, and the relative risk (RR) was 2.634 (95% confidence interval [CI]: 1.689–4.108). The 125 patients were further divided into three groups according to the cone depth (0–1.49 cm, 1.50–1.99 cm, and ≥2.00 cm) and cone volume (0–1.99 cm 3, 2.00–2.99 cm 3, and ≥3.00 cm 3). We analyzed the effects of LEEP with different cone depths and volumes, and found that with increased cone depth and volume, the RR of preterm birth increased [Table 2].{Table 2}

However, there were many confounding factors that would affect the preterm birth like maternal age at delivery, parity, gravidity, and the time interval between LEEP and the delivery. Thus, we used logistic regression model to do the multivariate analysis of the risk factors of preterm [Table 3]. In the multivariate analysis, the only risk factor of significant difference for preterm was cone volume (adjusted RR 1.708, 95% CI 1.131-2.580). The adjusted RR for cone depth was 2.869, but it was of no significant difference.{Table 3}

Of 125 patients in the LEEP group, 71 (56.8%) underwent CS, whereas 197 (39.4%) in the control group underwent CS. Compared with the control group, the rate of CS was obviously increased, and RR was 1.442 (95% CI 1.195-1.739). However, CS should be performed according to specific indications. In the 11 attending hospitals, the indications of CS are divided into maternal factors (including the presence of systemic disease or pregnancy complications, uterine scarring, or abnormalities of the birth canal or strength of uterine contractions), fetal factors (including fetal position, macrosomia, fetal distress, amniotic fluid contamination), and social and psychological factors. The indications for CS were compared between the 2 groups [Table 4]. And it seemed that the constituent ratio of the indications in the LEEP group was not significantly different from that of the control group.{Table 4}

Effects of loop electrosurgical excision procedure on sexual function

We divided the patients into three groups according to cone depth (0–1.49 cm, 1.50–1.99 cm, and ≥2.00 cm) cone volume (0–1.99 cm 3, 2.00–2.99 cm 3, and ≥ 3.00 cm 3). The baseline information was listed and compared [Table 5]. No significant differences were observed in any of the FSFI-19 dimensions, except for pain and total score. The score in the pain dimension of the group with cone depth ≥2.00 cm was significantly lower than those of the other two groups (P < 0.05), and the difference between the other two groups was not statistically significant (P > 0.05). Similarly, the score in the pain dimension and the total score of the group with cone volume ≥3.00 cm 3 were significantly lower than those of the other two groups (P < 0.05) and the differences between the others were not significant (P > 0.05) [Table 6].{Table 5}{Table 6}

 Discussion



Effects of loop electrosurgical excision procedure on fertility

Recent retrospective case–control studies have reported that LEEP increases the risk of postoperative preterm birth.[9] In our study, LEEP doubled the risk of preterm birth compared with that in the control group. LEEP increases the risk of preterm birth mainly because it resects part of the cervical tissue, leading to cervical dysfunction. Liverani et al. found that the increased cone depth plays a more important role than cone volume in increasing the risk of preterm birth. The depth of cervical excision using LEEP was negatively correlated with neonatal gestational age, but the cone volume and cross-sectional area of cervical excision using LEEP showed no significant negative correlations with gestational age. However, Jakobsson and Bruinsma found that the risk of preterm birth increased with increased volume or weight of cone tissue.[10] In our study, we found that the cone volume was the only risk factor of significant difference for preterm when we did the multivariate analysis, indicating that considering all of the confounders, cone volume plays the most important role in increasing the risk of preterm. In general, depth and volume reflected the injury caused by LEEP to cervical tissue. A greater degree of LEEP-induced cervical tissue injury corresponds to a higher risk of preterm birth.

In the multivariate analysis, the age at delivery, parity, gravidity, and the time interval between LEEP and delivery was of no significant difference. Most studies showed that the time of fertilization was not associated with the risk of preterm birth after LEEP.[11],[12] However, Ciavattini et al. found that the risk of preterm birth and abortion was significantly higher when the time of fertilization after LEEP was < 12 months; however, when the time of fertilization was >12 months, the risk of preterm birth was not significantly increased.[13] Song et al. found that the cervix recovers 93.1% of its original length and 94.3% of its original volume within 6 months after LEEP and reported that the length and volume of the cervix would not change after 6 months. Thus, delivery within 6 months after LEEP may lead to negative pregnancy outcomes.[14] In our study, we did not find the time of time interval to be a risk factor for preterm birth, probably because there were few cases with fertilization times < 6 months (9.48 ± 2.46 months). Therefore, to demonstrate whether a short time of fertilization will increase the risk of adverse pregnancy outcomes (preterm birth, abortion, preterm rupture of membranes, etc.), further study is necessary.

Kyrgiou et al. found an RR of 1.74 for preterm birth after a single cervical treatment and an RR of 2.81 after repeat cervical treatments,[15] indicating that repeated treatment will increase the risk of preterm birth. Castañon et al. also found that the increased risk of preterm birth is not restricted to the first birth after treatment and remains for the second and subsequent births.[16]

There are some explanations for the increased risk of preterm birth due to LEEP:

  1. Although LEEP is a relatively conservative treatment, it still excises part of the cervical tissue, affecting the mechanical support function of the cervix during pregnancy
  2. Scar tissue may form during the self-repair process after LEEP. The ability to regenerate the glands is limited in scar tissue, and the reduction in cervical glands will result in a reduction in mucus – an important component in the maintenance of the immune environment of the cervix and vagina. Consequently, the changes in the vaginal immune environment after LEEP may increase the possibility of retrograde infection by pathogens, making preterm rupture of membranes and preterm birth more likely.[17],[18]


Some previous studies also found that women with HSIL, regardless of whether LEEP is performed, have an increased risk of preterm birth compared to women without HSIL.[19],[20] However, due to ethical issues, interventions such as LEEP must be recommended to patients who are diagnosed with HSIL. Therefore, it is difficult to conduct a prospective randomized controlled study on the risk of preterm birth due to HSIL itself. In addition, in studying the risk of preterm birth caused by LEEP, some confounding factors that may affect the risk cannot be completely excluded from a study, such as gestational complications that may lead to preterm birth and the HPV infection itself may cause preterm birth by dysbacteriosis. Also, the original depth and volume of the cervix are important in estimating the risk of preterm birth after LEEP.

Leiman et al. suggested that LEEP may cause postoperative cervical stenosis and local scar formation, affecting the progress of labor and thereby increasing the failure of vaginal delivery and incidence of CS.[21] However, in recent studies, LEEP did not increase the risk of CS and cannot be an indication for CS.[22] In our study, the raw relative risk of CS was increased in the LEEP group, however the constituent ratio of the indications in the LEEP group was not significantly different from that of the control group. This suggested that LEEP did not raise the risk of any specific indication of CS and it might raise the risk of CS in all indications. This did not correspond to the former hypothesis raised by Leiman et al.[21] Also, there were not a standardized definition and classification for the indications of CS. There were multiple confounding factors in demonstrating the effect of LEEP on CS. These confounding factors cannot be completely eliminated, such as women who underwent CS may both have LEEP treatment, social and psychological factors, and whether her social and psychological factors are related to LEEP treatment cannot be stated clearly. Further study like collect the detailed labor record of the women with a history of LEEP to explore whether LEEP had effect on the dilation of cervix during labor.

There is no consensus on whether cervical cerclage should be routinely performed in LEEP patients to prevent preterm birth. Leiman et al. suggested that cervical cerclage should be advised for patients with cone depth >2 cm.[21] In this study, no patients underwent cervical cerclage due to cervical insufficiency after LEEP. Most studies have shown that preterm birth is related to the length of the cervix in the second trimester.[23] Therefore, we suggest that cervical cerclage should be implemented according to the length of the cervix in the second trimester to avoid overtreatment.

Sexual function after loop electrosurgical excision procedure

The effect of LEEP on sexual function mainly includes painful intercourse. We divided the patients into different groups according to cone depth and cone volume. No significant differences were observed between the groups in any of the dimensions except for pain. For the pain dimension, the scores of the group with cone depth >2.00 cm or cone volume >3.00 cm 3 were significantly lower than those of the other groups (P < 0.05). Because of the low scores in the pain dimension, the total scores were also the lowest in the group with cone depth >2.00 cm or cone volume >3.00 cm 3. This demonstrated a greater degree of LEEP-induced cervical tissue injury corresponded to greater pain in postoperative sexual intercourse and more negative effect on sexual function.

There is no consensus on the specific effects of LEEP on sexual function. Most studies have shown that the effects of LEEP on sexual function were negative, but limited. Serati et al. found that there were no obvious changes in sexual function except for sexual desire.[24] Inna et al. found that LEEP had negative effects on satisfaction, orgasm, and vaginal elasticity.[25] However, Sadoun et al. found that the scores for sexual desire and orgasm were higher after LEEP than those before surgery and explained this result by proposing that LEEP cured CIN and HPV infection, both of which have greater impacts on sexual life than the anatomical effects of LEEP.[26]

In our study, we could not conduct a self-control study due to the absence of assessments of sexual function before LEEP. Besides, sexual function involves not only a physical experience but also psychological, emotional, and social factors, and many other aspects. These factors could not be fetched by follow-up or medical record. Therefore, further prospective cohort studies are needed to investigate the effects of LEEP on sexual function, including self-control and case–control studies.

In summary, it is important to perform a Pap smear and colposcopy before recommending LEEP to patients. When LEEP is necessary, it is crucial to perform colposcopy and a Schiller's test to confirm the size of the lesion and to avoid excessive tissue removal. It is essential to provide guidance to patients after LEEP regarding fertility, especially regarding the risk of preterm birth to enable physical and psychological preparation. In addition, it is imperative to provide guidance to mitigate painful intercourse and improve sexual function.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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