Comparing Anti-Mullerian Hormone Levels after Laparoscopic Salpingectomy or Laparoscopic Salpingostomy in Tubal Ectopic Pregnancy

Ectopic pregnancy refers to the presence of an extrauterine gestational sac and is one of the most common medical emergencies in early pregnancy.[ 1 ] The condition can be treated if diagnosed timely, but it still exposes patients to tubal rupture and severe bleeding.[ 2 3 ] Ectopic pregnancy can be treated through surgery, watchful waiting, pharmacotherapy, and surgery. Each treatment method can be chosen based on the patient’s clinical conditions. In fact, the choice of treatment depends on the patient’s symptoms, the disease severity, the EP site, and the patient’s own choice.[ 4 ] Medical treatment with methotrexate is the preferred therapeutic option.[ 5 ] In patients with medical therapy failure, unsuitable for medical therapy or unstable hemodynamic condition, laparoscopy is the standard surgical approach. Laparoscopic salpingostomy or salpingectomy is the treatment methods that have been previously used for these patients that are associated with various benefits and complications.[ 6 ] Salpingectomy has a lower rate of persistent ectopic pregnancy than salpingostomy. The possible disadvantage of salpingectomy is a decrease in ovarian reserve because of disruption of utero-ovarian circulation.[ 7 8 9 10 ] Anti-Mullerian hormone (AMH) is a glycoprotein belonging to the transforming growth factor (TGF-β) produced by the growing granulosa cells of small follicles.[ 11 ] Serum levels of AMH, produced by early follicle granulosa cells, are independent of gonadotropins and are therefore relatively constant in each cycle and between menstrual cycles. Therefore, the level of AMH has been accepted as a reliable and objective indicator for determining ovarian reserve.[ 12 ] Studies have shown that AMH is a reliable factor for examining ovarian reserve.[ 13 ] As the effect of surgery on AMH levels and ovarian reserve varies, the present study aimed to evaluate the effect of salpingectomy and salpingostomy on ovarian reserve through measuring serum levels of AMH.

A total of 64 women participated in the study; 32 underwent salpingectomy and 32 underwent salpingostomy. The characteristics of patients are depicted in Table 1 . The mean maternal age in the salpingectomy group (31.87 ± 4.85) was significantly higher than the salpingostomy group (29.48 ± 4.16) ( P = 0.040). In addition, the number of pregnancies in the salpingectomy group (2.62 ± 1.21) was significantly higher than in the salpingostomy group (1.93 ± 0.99) ( P = 0.017). There was no significant difference in the levels of β-hCG and duration of pregnancy between the groups ( P > 0.05) [ Table 1 ]. Comparison of demographics in salpingectomy and salpingostomy groups The relationship between AMH and maternal age was inverse and nonsignificant (r = -0.133, P value = 0.376). In contrast, AMH has a direct and nonsignificant relationship with gestational age (r = 0.146), number of pregnancies (r = 0.036), and BHCG level (r = 0.068) ( P value > 0.05) [ Table 2 ]. The relationship between AMH and the basic characteristics of the studied women The mean level of postoperative AMH in the salpingostomy group (3.27 ± 1.44) was significantly higher than the salpingectomy group (2.80 ± 1.47) ( p group = 0.013). There was no significant difference between the mean levels of AMH before and three months after surgery in both salpingectomy and salpingostomy groups ( p time > 0.05) [ Table 3 ]. A significant interaction existed between the time effect and group ( p time*group = 0.043), indicating that the trend of AMH changes during three months after surgery in the two groups was different. Descriptive indicators and comparison of preoperative and postoperative levels of AMH in the two groups *Adjusted by AMH before surgery, maternal age, gestational age, number of pregnancies, and BHCG

The present study aimed to evaluate and compare the effects of laparoscopic salpingostomy and salpingectomy on anti-Mullerian hormone levels in patients with ectopic pregnancy. None of these procedures had a significant reducing effect on the postoperative levels of AMH. However, postoperative serum levels of AMH were higher in patients with salpingostomy than in the salpingectomy group. There are controversial study results in the literature. Some authors have reported that salpingectomy reduces the ovarian blood supply and compromises ovarian reserve[ 10 14 ] aiming to investigate the effect of salpingectomy on the ovarian reserve, 83 patients underwent unilateral salpingectomy, 41 patients underwent bilateral surgery, and 74 patients had no surgery. Serum levels of AMH were higher in patients who did not undergo surgery compared to the other two groups. The results of this study showed that salpingectomy has a negative effect on ovarian reserve; this was not confirmed in the present study, but its results showed that AMH levels were not correlated with the number of oocytes or age in patients treated through surgery.[ 14 ] On the contrary, Lin et al .[ 13 ] proposed that salpingectomy has no effect on ovarian reserve. In another study, investigated the effect of salpingectomy on preoperative and postoperative AMH changes in EP patients, it was found that salpingectomy had no short-term effect on the serum levels of AMH, and changes in AMH levels are independent of age, time of follow-up, and preoperative AMH serum levels.[ 15 ] In addition, this study found that six-month AMH biodiversity is less than 30%; this is largely consistent with our study. In addition, the results obtained by Sahin Ersoy G et al. [ 16 ] were similar with those of the present study. They aimed to compare the long-term effects of methotrexate and salpingectomy on the ovarian reserve in terms of AMH and showed that in the treatment of EP, neither administration of single-dose methotrexate nor salpingectomy had a permanent effect on ovarian reserve; serum levels of AMH and AFC were unchangeable in long-term after methotrexate doses or salpingectomy. However, the results of the present study showed a significant inverse relationship between postoperative levels of AMH and maternal age in patients undergoing surgery which can be due to the difference in samples and also the follow-up duration. In a recent article by Asgari et al. [ 17 ] on the effect of laparoscopic salpingostomy and salpingectomy on ovarian reserve in patients with EP, 93 patients were enrolled, of whom 46 underwent laparoscopic salpingectomy and 47 underwent laparoscopic salpingectomy, and AMH levels were measured before surgery and three months after surgery. They found no significant changes in AMH levels before surgery and three months after surgery; this was consistent with the results of the present study. In infertile women with hydrosalpinx tube or endometriosis of tube or adhered tube to ovary, compromise blood supply of ovary and decrease ovarian reserve probably predictable after salpingectomy. On the other hand, in hysterectomy patients after bilateral salpingectomy due to the separation of both ovaries from the uterus, a decrease in ovarian reserve may be expected. So, the reason for salpingectomy is very important. In the normal anatomy of the tube, salpingectomy has a less destructive effect on ovarian circulation due to the easy angle of access in the placement of the electrosurgical device. This study has limitations, such as the sample size, which was small. A larger sample size, a longer patient follow-up period, and a randomized study design would strengthen the study. However, the study’s advantages include comparable mean gestational age of patients and β-hCG levels before surgery in both groups.

Salpingostomy did not significantly change serum levels of AMH three months after surgery. However, postoperative serum levels of AMH were higher in patients with salpingostomy than in the salpingectomy group, and in fact, salpingostomy is a safer method. There was also an inverse relationship between maternal age and AMH levels and a direct relationship between gestational age and AMH levels. The results of this study showed that salpingectomy resulted in a slight decrease in serum levels of AMH, which was not statistically significant. The Institutional Review Board and Ethics Committee of the Isfahan University of Medical Science approved the study (IR.MUI.MED.REC.1397.041). An informed written consent was taken from each participant prior to the study enrollment. The study was registered in the Iranian Registry of Clinical Trials ( www.IRCT.ir ) by the number of IRCT2014123118866N4. There are no conflicts of interest.

This cross-sectional study was conducted at Alzahra and Beheshti Hospitals, Isfahan, Iran, from October 2017 to March 2019. Women with certain conditions, such as larger than 4 cm masses or β-hCG levels exceeding 5000 IU/ml, tubal ectopic pregnancy with fetal cardiac activity, and heterotopic pregnancy, are not candidates for methotrexate therapy. Additionally, individuals with sensitivities to methotrexate, as well as those with renal, hepatic, or pulmonary diseases, immunocompromised states, peptic ulcers, and hematologic diseases, should also avoid this treatment option. Inclusion criteria for salpingostomy (incision on the tube to remove pregnancy products) were intending pregnancy in the future, no tubal rupture, lack of tube serosa damage, and healthy contralateral tube, and inclusion criteria for salpingectomy were tubal rupture, moderate or severe tube injury, perioperative uncontrollable tube bleeding, extra-tubal pregnancy diameter of ≥4 cm, not intending another child, candidate for IVF, and recurrence of EP in a tube with a previous EP. Exclusion criteria were smoking, gynecological disorders affecting ovarian function such as endometriosis, previous tubal or ovarian surgery, history of infertility treatment or systemic chemotherapy, malignancy, autoimmune diseases, pelvic infection, vegetarian diet, methotrexate consumption, no access to the patient after three months, death, and no consent to continue the study. Patients could withdraw the study at any time. According to the sample size formula for comparison of the means, the required sample size was estimated 63 women, but due to the limited number of patients, the subjects were sampled through the consensus method to reach the sample size; therefore, all patients who met the inclusion criteria were enrolled from October 2017 to March 2019. Clinical information was collected through a checklist. Patients with confirmed diagnosis of ectopic pregnancy were enrolled in the study. Based on clinical conditions and specialist diagnosis, patients underwent laparoscopic salpingectomy or salpingostomy, thus randomization was impossible. The ideal surgical approach depends on the patient’s history, future fertility desires, and intraoperative findings. After entering the abdominopelvic cavity via laparoscopic approach, salpingectomy was implemented in patients with tubal ruptured, recurrent ectopic pregnancy in the same tube, sever damage tube, or ectopic pregnancy in a woman who has completed childbearing. Other patient’s salpingostomy was considered as a selective therapeutic approach. One hour before laparoscopy, blood samples were collected for AMH level testing. Surgical procedure was performed by a team of expert surgeons from Laparoscopic Center of Isfahan University of Medical sciences. After establishment of pneumoperitoneum with the Verres needle (Ethicon Endo-surgery Inc., USA) through vertical 10-mm subumbilical incision, a 10-mm laparoscope was introduced. Then, two 5-mm trocars were placed for operative instruments. Intra-abdominal CO2 pressure was set to 13–15 mmHg. Salpingectomy was performed through the bipolar method close to mesosalpinx to preserve ovarian vessel (40 W current; Richard Wolf, Germany). In patients undergoing salpingostomy, monopolar instrument was used to incise the antimesenteric edge of the tube to remove the ectopic trophoblast. After adequate irrigation, coagulation of tube was done with bipolar electrocoagulation, if needed. β-hCG was measured on the first day after surgery and then weekly until it reached normal levels. Serum AMH level was measured by a commercially available enzyme-like immunosorbent assay kit (ELISA; Beckman Coulter INC., Ireland) and reported as nanograms per milliliter with the detection limit of 0.16 ng/mL. The intraassay and intraassay coefficients of variation (CV) were 12.3 and 14.2%. AMH levels were measured in patients before surgery and three months after surgery and recorded in the checklist. Changes in the levels of AMH were assessed before and after surgery. Data were analyzed using SPSS version 18 (SPSS Inc., Chicago, IL, USA). Differences between baseline characteristics of patients were compared using the Chi-square test for categories and the independent sample t test for continuous variables. To compare the level of AMH between the two groups and the trend of its changes by adjusting the confounding factors, the repeated measures ANOVA was used. Also, Pearson’s correlation coefficient was used to evaluate the relationship between the postoperative AMH level and the basic characteristics of the patients. In all analyses, a significance level of less than 0.05 was considered.