The effects of conservative and surgical approaches in tubal ectopic pregnancy on fertility

Abstract

BACKGROUND:

Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to its effectiveness, the main concern is to limit the risk of relapse and preserve fertility.

OBJECTIVES:

Determine the impact of medical or surgical treatment for ectopic pregnancy on future fertility.

DESIGN:

Retrospective

SETTING:

Department of obstrtrics and gynecolgy at Ankara Etlik Zübeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey

PATIENTS AND METHODS:

Patients who were treated for ectopic pregnancy between June 2016 and November 2019 were allocated into two groups. Expectant approach or medical treatment by methotrexate constituted the conservative treatment group while salpingectomy by laparoscopy indicated the surgical treatment group.

MAIN OUTCOME MEASURES:

Fertility rates within two years following treatment were evaluated according to treatment options.

SAMPLE SIZE:

202 patients

RESULTS:

Of the 202 patients, 128 had medical treatment and 74 patients had surgical treatment for ectopic pregnancy. Of 272 diagnosed with ectopic pregnancy, 70 were excluded for various reasons. Parity and unemployment rate was significantly higher in the surgical treatment (P=.006 and P=.12, respectively). Moreover, ectopic mass size and serum β-hCG levels were significantly higher in the surgical treatment group (P<.001 and P<.001, respectively). There were no significant differences between the conservative and surgical treatment groups in time to pregnancy (17.0 months vs 19.0 months, P=.255). Similarly, there was no significant difference between the conservative and surgical treatment groups with respect to history of infertility (P=.12). There were no significant differences between the conservative and surgical treatment groups in terms of live birth (51.6% vs 44.6%) and ectopic pregnancy (2.3% vs 1.4%) (P=.72 for both). There was no significant difference between the conservative and surgical treatment groups with respect to infertility rate (35.9% vs 41.9%, P=.72) and admittance to the IVF program (3.9% vs 6.8%, P=.39) following ectopic pregnancy treatment.

CONCLUSIONS:

Reproductive outcomes did not differ significantly in women undergoing expectant management, medical treatment, and surgery for ectopic pregnancy. This finding suggests that clinicians should not hesitate to act in favor of surgical treatment for ectopic pregnancy even if there were concerns for future fertility.

LIMITATIONS:

Retrospective study.

INTRODUCTION

Ectopic pregnancy is to the implantation of a fertilized ovum outside the uterine cavity. Ectopic pregnancies are often seen in the Fallopian tubes, especially in their ampulla region.¹ Ectopic pregnancy accounts for 1-2% of all pregnancies.² However, the prevalence of ectopic pregnancy has significantly increased in recent years. This significant increase has been attributed to the rise in the use of intrauterine devices, the elevation in the frequency of pelvic infections and tubal reconstructive surgeries, and the widespread implementation of assisted reproductive techniques. Despite this increase, mortality related to ectopic pregnancy has decreased. This decrease is due to the ability to make the diagnosis of ectopic pregnancy as early as possible with serial beta human chorionic gonadotropin (β-hCG) measurements and transvaginal ultrasonography.^3–5

The management of ectopic pregnancy includes the expectant approach, medical treatment, and surgery. These treatment options should allow the efficient treatment of ectopic pregnancy besides limiting the risk of relapse and preserving fertility. Patients who undergo treatment for ectopic pregnancy commonly are concerned about future fertility. Yet, the studies related to the reproductive outcomes of patients undergoing treatment for ectopic pregnancy have yielded controversial results.^1–5 Therefore, this study was designed to investigate the subsequent fertility rate in women who had medical or surgical treatment for ectopic pregnancy at a tertiary health center.

PATIENTS AND METHODS

This was a cross-sectional review of patients who were treated for ectopic pregnancy at Ankara Etlik Zübeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey between June 2016 and November 2019. The study protocol was approved by the local ethics committee and written informed consent was obtained from each participant. The diagnosis of ectopic pregnancy was made by serial β-hCG measurements and transvaginal ultrasonography findings. This diagnosis was confirmed by histopathological examination.

All data, including age, obstetric history, body mass index, smoking, education level, employment status, β-hCG levels, ultrasonography findings and treatment were obtained from hospital records. All patients who underwent treatment for ectopic pregnancy were contacted by telephone after two years and their fertility status was noted.

The patients included in this study were allocated into two groups based on their treatment. Expectant approach or medical treatment by methotrexate constituted the conservative treatment group while salpingectomy by laparoscopy was the surgical treatment group.

Data were analyzed by IBM SPSS version 20.0 (IBM Corp., Armonk, NY, USA). The Kolmogorov-Smirnov test was used to test the data distribution. Continuous variables with a normal distribution (age and body mass index) were compared by the Student t-test, whereas continuous variables not normally distributed (gravidity, parity, ectopic mass size, β-hCG and time to pregnancy) were compared by the Mann-Whitney U test. Continuous variables with a normal distribution are denoted as mean and standard deviation, and continuous variables not normally distributed are expressed as median and 25th-75th percentiles. Categorical variables were compared by the chi square test and expressed as numbers and percentages. Two-tailed P values <.05 were accepted as statistically significant.

RESULTS

Of 272 patients identified as having ectopic pregnancy, 202 patients were included in this study (Figure 1). Seventy were excluded because they had previous tubal surgery (n=4), they wanted contraception (n=22), they were diagnosed with ectopic pregnancy after in vitro fertilization (IVF) treatment (n=3), they had a history of ectopic pregnancy (n=6), or they could not be contacted by telephone (n=35). The conservative and surgical treatment groups were statistically similar with respect to age, gravidity, and body mass index (P=.10, P=.13 and P=.944, respectively) (Table 1). However, parity was significantly higher in the surgical treatment group than in the conservative treatment group (P=.006). Moreover, ectopic mass size and serum β-hCG levels were significantly higher in the surgical treatment group than the conservative treatment group (P<.001 and P<.001, respectively). There were no significant differences between the conservative and surgical treatment groups with respect to time to pregnancy (17.0 months vs 19.0 months, P=.255).

Figure 1.

Patient flow diagram

Table 1.

Demographic characteristics and clinical findings (n=202).

	Conservative treatment (n=128)	Surgical treatment (n=74)	P
Age	29.3 (5.6)	30.7 (5.3)	.10a
Body mass index (kg/m2)	26.2 (4.1)	26.2 (4.1)	.944a
Gravidity	3.0 (2.0–4.0)	3.0 (2.0–4.0)	.13b
Parity	1.0 (0–2.0)	1.0 (0–2.0)	.006b
Ectopic mass size (mm)	15.0 (13.0–17.0)	27.0 (20.0–34.0)	<.001b
β –hCG (mIU/mL)	421.0 (112.0–1119.0)	1113.0 (213.0–3243.0)	<.001b
Time to pregnancy (months)	17.0 (11.0–23.0)	19.0 (11.0–27.0)	.255b

Data are mean (standard deviation) or median (25th-75th percentile).

^aStudent t-test;

^bMann-Whitney U test.

The conservative and surgical treatment groups were statistically similar in terms of education levels and smoking (P=.82 and P=.92, respectively) (Table 2). The unemployment rate was significantly higher in the surgical treatment group (P=.002). There was no significant difference between the conservative and surgical treatment groups with respect to history of infertility (P=.12). The conservative and surgical treatment groups were statistically similar with respect to live births (51.6% vs 44.6%) and ectopic pregnancies (2.3% vs 1.4%) (P=.72 for both). There was no significant difference between the conservative and surgical treatment groups in infertility (35.9% vs 41.9%, P=.72) or admittance to the IVF program (3.9% vs 6.8%, P=.39) following ectopic pregnancy treatment.

Table 2.

Demographic characteristics and reproductive outcomes (n=202).

	Conservative treatment (n=128)	Surgical treatment (n=74)	P
Education
Illiterate	2 (1.6)	2 (2.7)	.82
Primary-Hig school	112 (87.5)	65 (87.8)
University	14 (10.9)	7 (9.5)
Smoking
No	77 (60.2)	44 (59.5)	.92
Yes	51 (39.8)	30 (40.5)
Employed
No	73 (57.0)	58 (78.4)	.002c
Yes	55 (43.0)	16 (21.6)
Previous infertility
No	115 (89.9)	71 (95.9)	.12
Yes	13 (10.1)	3 (4.1)
Pregnancy
None	46 (35.9)	31 (41.9)	.72
Miscarriage	13 (10.2)	9 (12.1)
Ectopic	3 (2.3)	1 (1.4)
Live birth	66 (51.6)	33 (44.6)
Assisted reproduction
None	118 (92.2)	66 (89.1)	.39
CC-IUIa	5 (3.9)	2 (2.7)
COH-IUIb	0 (0.0)	1 (1.4)
IVF	5 (3.9)	5 (6.8)

Data are number (percentage).

^aCC-IUI: clomiphene citrate intrauterine insemination;

^bCOH-IUI: controlled ovarian hyperstimulation and intrauterine insemination. Statistical analysis by chi-square test. Other variables by the Mann-Whitney U test

DISCUSSION

The etiopathogenesis of ectopic pregnancy has not been fully understood, but the most important risk factors for this pathology comprise a previous history of ectopic pregnancy, a previous history of pelvic inflammatory disease, the use of an intrauterine device, a history of tubal surgery, infertility, and smoking.⁶ The present study was designed to investigate the impact of medical or surgical treatment for ectopic pregnancy on future fertility by assessing reproductive outcomes.

The mean age of the cohort was 29.8 years. This number complies with other studies, as population-based studies report that the majority of ectopic pregnancies occur in women aged between 25 and 35 years.^7,8 In addition, the study cohort had a smoking prevalence of 40.4% and about 8% of the recruited patients had a history of infertility. These findings were in contrast to previously published studies, which address smoking and a previous history of infertility as risk factors for ectopic pregnancy.^7,8

Recent advances in the early diagnosis of ectopic pregnancy have led to a significant decrease in morbidity and mortality.^3,5 Moreover, such an advance has provided the opportunity for applying conservative treatment instead of surgical treatment. That is, expectant management or medical treatment can be performed as first line in patients with stable hemodynamics, no acute abdominal findings, no fetal cardiac activity in the ectopic focus, serum β-hCG levels <10 000 IU/mL, or an ectopic pregnancy size <4 cm.

In our study, 7.4% of the patients were treated with the expectant approach, 55.9% of the patients received methotrexate treatment, and 36.6% were treated surgically. The cumulative success rate in the conservative treatment group was 95.7%. In a prospective study involving 495 patients with ectopic pregnancy who were treated with a single dose of methotrexate, the success rate was reported as 90.5%.⁹ Serum β-hCG levels and ectopic pregnancy mass size were significantly higher in the surgical treatment group (P<.001 for both). This significant difference can be attributed to the selection of patients according to the factors that predict the success of treatment applied for ectopic pregnancy. The factors that determine the success of methotrexate treatment for ectopic pregnancy include serum β-hCG concentration, the size of the ectopic pregnancy, fetal cardiac activity, and free intraperitoneal fluid.

At the study center, laparoscopic salpingectomy is routinely performed in patients undergoing surgical treatment for ectopic pregnancy. The main reason why laparoscopic salpingostomy is not preferred is the potential inconvenience of controlling tubal bleeding. Additionally, there is a potential for residual trophoblast retention, and a risk of recurrence for ectopic pregnancy in the preserved tube. Since prior studies have failed to detect significant differences between laparoscopic salpingostomy and laparoscopic salpingectomy with respect to subsequent fertility, laparoscopic salpingectomy has been preferred over laparoscopic salpingostomy for the treatment of ectopic pregnancy.^10–13

The present study was unable to find a significant difference between the fertility rates of patients who underwent conservative and surgical treatment for ectopic pregnancy. The conservative and surgical treatment groups were statistically similar with respect to live births (51.6% vs 44.6%, P=.72). A similar study in Turkey examined the fertility rates in a cohort of 119 women who underwent treatment for ectopic pregnancy. However, there was no significant difference between the rates of clinical pregnancy after medical treatment, conservative surgery, and radical surgery (69% vs 65% vs 60%).¹⁴ These findings are in accordance with other published data.¹⁵

The power of the present study was limited by its cross-sectional design, relatively small cohort size and heterogeneity in cohort characteristics. The significantly higher parity in the surgical treatment group might have also caused a bias in subsequent fertility of the patients. In conclusion, reproductive outcomes did not differ significantly in women undergoing expectant management, medical treatment, or surgery for ectopic pregnancy. This finding suggests that clinicians should not hesitate to use surgical treatment for ectopic pregnancy even if there are concerns for future fertility. Further research is warranted to clarify the reproductive outcomes related expectant management, medical treatment and surgery in women diagnosed with ectopic pregnancy.

Funding Statement

None.