Decline in βhCG levels between days 0 and 4 after a single dose of methotrexate for ectopic pregnancy predicts treatment success: a retrospective cohort study

In current protocols for the medical management of ectopic pregnancies, the first indication of treatment response is obtained no sooner than day 7. We examined whether human chorionic gonadotrophin (βhCG) trends between days 0 and 4 after methotrexate provide an earlier indication of the likely outcome. Of 33 patients where serum βhCG dropped between days 0 and 4 after methotrexate, the ectopic pregnancy was resolved in 88% of cases without further treatment. Of 12 women where serum βhCG rose between days 0 and 4, only 42% had treatment success. A fall in βhCG between days 0 and 4 after treatment with methotrexate for ectopic pregnancy predicts a high likelihood of treatment success.     

Do serum beta-human chorionic gonadotropin levels on day 4 following methotrexate treatment of patients with ectopic pregnancy predict successful single-dose therapy?

The purpose of this study is to assess whether serum beta-human chorionic gonadotropin (beta-hCG) levels on day 4 following methotrexate (MTX) treatment in patients with ectopic pregnancy predict successful single-dose therapy or the need for subsequent surgical intervention. Retrospective analysis of patients with ectopic pregnancies treated with MTX (50 mg/m (2)) was conducted. Inclusion criteria for MTX management were serum beta-hCG < 15,000 mU/mL, absent fetal cardiac activity, ultrasonographic gestational sac < 3.5 cm, normal liver function tests, hemodynamically stable patient with no evidence of hemoperitoneum, and informed consent. Day 1, 4, and 7 serum beta-hCG levels were obtained. Outcome parameters included successful single-dose MTX management, the requirement for multiple treatments, and whether subsequent surgery was required. Receiver operator characteristic (ROC) curves were used. P < 0.05 was considered significant throughout. Eighty-three patients were studied. Of these, 60 patients were treated successfully with single doses, 16 patients required two doses, and two patients required three doses of MTX, and five underwent surgical management. Mean day 1 serum beta-hCG levels of patients successfully treated with single-dose MTX was 3938.5 (+/- 589.2 [standard deviation]) versus 1767.65 (+/- 1237.8) mU/mL in patients requiring multiple doses of MTX therapy, ( P < 0.0001). ROC curves for serum beta-hCG levels on days 1, 4, and 7 were 0.449, 0.592, and 0.754, respectively, indicating that only day 7 serum beta-hCG levels were associated with successful single-dose MTX therapy. Serum beta-hCG levels on day 4 of MTX in patients with ectopic pregnancy do not predict successful single-dose therapy or the need for surgery.     

The dilemma of recurrent ectopic pregnancy after tubal surgery and in-vitro fertilization. What to do?

This commentary was written to stimulate a debate on the role of tubal surgery for ectopic pregnancy in women undergoing IVF.     

Can sonographic endometrial pattern be an early indicator for tubal ectopic pregnancy and related tubal rupture?

Purpose  

The present study aims to determine whether sonographic endometrial pattern can be addressed as an early indicator for tubal ectopic pregnancy and related tubal rupture in case ultrasonography reveals no adnexal mass and maternal serum beta human chorionic gonadotropin (HCG) level is below the discriminatory zone (≤1,000 mIU/mL).     

Laparoscopic tubal surgery for ectopic pregnancy: trainees’ perspective in the UK

Ectopic pregnancies (EP) account for approximately 1% of all pregnancies. Surgical management of such patients should be accomplished through the laparoscopic route. Presently, available data from national studies suggest that only a minority of women benefit from such an approach. Regional studies and single institution reports suggest that trainee involvement in these procedures vary widely. Competency in laparoscopic surgery for EP is a mandatory requirement for independent practice in the UK. In a recent survey of UK trainees of all grades in obstetrics and gynaecology, 53.4% of trainees reported that they were trained or being trained in such procedures. This study examines the perspectives of the trainees. We performed a national questionnaire survey of intermediate- and advanced-level trainees in the UK During a 12-month period, 52% of trainees had performed at least one procedure independently; 80% of trainees performed most of the procedure on at least one occasion. The satisfaction with training was rated as 3 on a five-point Likert scale. Thirty percent of the trainees had access to a laparoscopy simulator. We found a high level of trainee engagement with laparoscopic tubal surgery. The intensity of experience is likely inadequate to satisfy the learning curve. A holistic approach s required to ensure surgical competence.     

How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data

OBJECTIVE: We analyzed human chorionic gonadotropin (hCG) follow-up data of patients with molar pregnancy. Women often do not complete recommended post-disease screening. Our purpose was to determine if continuing follow up of uncomplicated molar cases beyond attaining undetectable hCG levels is necessary for detecting relapse of gestational trophoblastic disease. STUDY DESIGN: One hundred fifty patients treated at Hungarian National Health Center were analyzed. Those who developed persistent disease before hCG had become undetectable were excluded from further analysis (n=24; 16%). RESULTS: Among 126 uncomplicated cases, 72 patients (57%) completed follow up, and 54 (43%) discontinued their protocol before it had been completed. Of 120 patients who achieved at least one undetectable hCG level, none had any evidence of relapse. CONCLUSION: In uncomplicated hydatidiform mole, our analysis indicates that once undetectable serum hCG levels are attained, relapse is unlikely. Although further monthly checks are advisable, the likelihood of recurrence appears very low.     

Early diagnosis of ectopic pregnancy. Does use of a strict algorithm decrease the incidence of tubal rupture?

OBJECTIVE: To determine if tubal rupture rates are decreased when a strict diagnostic algorithm is employed in the evaluation of women with suspected ectopic pregnancy as compared to individualized diagnostic methods. STUDY DESIGN: Between 1994 and 1996, a group of investigators at Charleston Area Medical Center employed a strict diagnostic algorithm consisting of serum quantitative human chorionic gonadotropin (hCG) levels, progesterone levels, ultrasound and endometrial curettage in order to expedite diagnosis when ectopic pregnancy was suspected (group A patients). Other practitioners employed traditional criteria in similar clinical situations (group B patients). Medical records of patients diagnosed with ectopic pregnancy in this period were retrospectively reviewed. Demographic data, clinical and laboratory characteristics, and rate of tubal rupture were compared. RESULTS: Sixty-one of 122 patients were diagnosed with ectopic pregnancy by strict criteria. These patients did not differ significantly from those evaluated by an individualized approach in regard to age, gravidity, parity or risk factors for ectopic pregnancy. Menstrual age, hCG levels and progesterone levels were similar as well. Group A patients had a median diagnostic interval of 2 days, with a range of 0-16. Group B patients had a median diagnostic interval of 8 days, with a range of 0-44 (P < .001). Of patients evaluated by this strict algorithm, 3.3% experienced rupture as compared to 23% of patients in group B (P < .001). CONCLUSION: Use of a strict diagnostic algorithm in the evaluation of patients with suspected ectopic pregnancy resulted in decreased tubal rupture rates. Such an algorithm could be disseminated to all locations for triage of patients and use in a standardized manner. This practice could result in a reduction in loss of reproductive function and mortality secondary to ectopic pregnancy.     

Trichosanthin, a Chinese medicine for the medical treatment of ectopic pregnancy with high levels of β-hCG

This was a retrospective study of the effectiveness of trichosanthin (TCS), an active component isolated from the Chinese herb root tuber of Trichosanthes kirilowii on 140 cases of ectopic pregnancy with higher levels of β-human chorionic gonadotropin (β-hCG) managed with a single dose of TCS treatment. Trichosanthin has been used for medical treatment of ectopic pregnancy in China since the 1980s. This study was performed in a major teaching hospitals in China. The mean pretreatment level of β-hCG in the TCS treatment group was 3387.57 IU/L. The success rate of TCS treatment was 85% (119 of 140) which was similar to methotrexate (MTX) treatment. In 86 women with a high level of β-hCG (over 2000 IU/L), the success rate was 80.08% when treated with TCS. Of this group, 26 women who had a high level of β-hCG (over 5000 IU/L) showed a success rate of 73%. The level of β-hCG on days 4, 7, and 10 in TCS group was significantly decreased. This study has shown that TCS may be an option for the medical treatment of unruptured ectopic pregnancy or an option for the treatment of ectopic pregnancy with higher levels of β-hCG than currently recommended for medical management with MTX.     

Conservative treatment of ectopic pregnancy with methotrexate in a nonoperable patient with Crohn’s disease

We present a case of conservative management using methotrexate for ectopic pregnancy in a nonoperable patient with complicated severe Crohns disease. This case demonstrates the successful use of methotrexate in an unusual situation in which laparoscopy or laparotomy could have further jeopardised the patients medical status.     

Can we predict patients at risk for persistent ectopic pregnancy after laparoscopic salpingotomy?

To identify factors that may predict patients at increased risk for persistent ectopic pregnancy after linear salpingotomy, we analyzed demographic, surgical, and biochemical variables retrospectively in 60 women who underwent laparoscopic linear salpingotomy, and compared data in those who developed persistent ectopic pregnancy (study group) versus those who were cured (controls). The two groups were similar with respect to demographic features and surgical findings. They did not differ significantly in gestational age and human chorionic gonadotropin (hCG) levels at time of surgery. There was, however, a significant difference in hCG dynamics when the average daily increase in the week before surgery was analyzed. Eleven (18%) women developed persistent ectopic pregnancy. The disorder did not occur in those whose hCG levels were flat or declining, whereas patients whose levels increased more than 40% per day had a significantly greater risk. In addition, at surgery, tubal bleeding was significantly more common in study patients than in controls (55 vs 9%, p<0.001). We conclude that hCG dynamics in the week before salpingotomy, and bleeding activity at surgery may identify patients who are the most likely candidates for persistent ectopic pregnancy.     

Comparison of the long-term effects of single-dose methotrexate and salpingectomy on ovarian reserve in terms of anti-müllerian hormone levels

The aim of this study was to compare the effects of single-dose methotrexate (MTX) and salpingectomy on ovarian reserve in women with ectopic pregnancy in the late post-treatment period. A total of 181 patients were included in the study; 56 of them received a single-dose of MTX, 45 of them had undergone salpingectomy treatment for ectopic pregnancy in the previous 12–18 months, and 80 healthy women constituted an age-matched control group. The anti-müllerian hormone (AMH), follicle stimulating hormone (FSH) and oestrogen (E₂) levels, as well as antral follicle counts (AFC) of the patients were evaluated. The average age was similar in both groups (p?=?0.094) and there was no statistically significant difference in the smoking status of the patients (p?=?0.949). None of the three groups displayed a significant difference in terms of AFC (p?=?0.528), AMH (p?=?0.147), FSH (p?=?0.393) and E₂ levels (p?=?0.117). In the treatment of ectopic pregnancy neither the single-dose MTX application nor the salpingectomy had any permanent detrimental effect on the ovarian reserve; serum AMH levels and AFC are unaltered in the long term following single-dose MTX or salpingectomy.     

Increment in β-hCG in the 48-h period prior to treatment: a new variable predictive of therapeutic success in the treatment of ectopic pregnancy with methotrexate

Objectives To evaluate the efficacy of oral progestogen, chlormadinone acetate, and intramuscular (IM) progesterone for luteal support in patients, undergoing assisted reproductive technology (ART) treatment, who were treated with a gonadotropin-releasing hormone agonist (GnRHa). Methods This was a prospective randomized study of 40 patients with normal and high response (serum estradiol > 2,000 pg/ml) in GnRHa down-regulation. Patients were randomized to receive either oral chlormadinone acetate or IM progesterone. The outcomes of ART treatment, including pregnancy and embryo implantation rates, were analyzed. Results There were no significant differences in the clinical pregnancy rates (25 vs. 20%) and in the implantation rates (12.7 vs. 9.1%) of patients who received IM progesterone and oral chlormadinone acetate. Endometrial thickness was also comparable between oral chlormadinone acetate and IM progesterone. Conclusion Oral progestogen, chlormadinone acetate showed a comparable pregnancy rate and live birth rate with IM progesterone as luteal support for the high responders. The optimal methods for luteal support may be dependent on responses to stimulation with gonadotropin, although it is not concluded that oral chlormadinone acetate is recommended as an option for luteal support in high responders.     

Comparison of two misoprostol regimens for mid-trimester pregnancy terminations after FIGO’s misoprostol dosage recommendation in 2012

Objective: To compare the safety and efficacy of two misoprostol regimens for mid-trimester pregnancy terminations.

Methods: Retrospective analysis of 263 cases of pregnancy terminations with misoprostol between 12 and 24 weeks was performed. Group 1 (total 129 patients) consisted of patients who were given 200?mcg vaginal misoprostol every 4?h until the abortion, whereas Group 2 patients (total 134 patients) were given misoprostol as in International Federation of Gynecology and Obstetrics’s (FIGO) 2012 recommendation. In case of a previous cesarean section doses were halved in both groups. Primary outcomes of the study were the time to abortion and the total drug dose used. Secondary outcome was the rate of complications.

Results: Total dose and time to abortion did not differ between the groups. As for complications, one patient (%0.8) in group 1 developed HELLP syndrome and had hysterotomy. One patient (%0.8) in group 2 had uterine rupture and had total hysterectomy. Two patients in both groups considered failure of induction and terminated with surgery (hysterotomy). Groups did not show difference in induction failure rates.

Conclusions: We respect the presence of dose recommendation stated by the FIGO and found similar results with our recent protocol. Other misoprostol regimens used worldwide should also be compared with this guideline in order to improve its efficacy.     

Networks of E-cadherin, β1 integrin,and focal adhesion kinase in the pathogenesis of tubal pregnancy

E-cadherin, β1 integrin, and focal adhesion kinase (FAK) are reported to involved in eutopic implantation by mediating cell adhesion. However, less is documented about their roles in ectopic implantation. This study was undertaken to evaluate the roles and networks of E-cadherin, β1 integrin, and FAK in tubal pregnancy. A total of 31 Fallopian tube specimens were obtained from tubal pregnant women. Immunohistochemistry and western blot were used to analyze the distributions and levels of E-cadherin, β1 integrin and phosphorylated-FAK (Pho-FAK) in the Fallopian tube epithelium. Normal Fallopian tube samples derived from non-pregnant women with benign genital diseases were used for comparison. E-cadherin presented in the cytomembrane of tubal epithelial cells and β1 integrin mainly expressed in the cytoplasm. A lowest-level of E-cadherin was detected in the implantation site (0.63?±?0.29) when compared with the non-implantation site (0.95?±?0.37) and the controls (0.89?±?0.33) (P?<?0.05). β1 integrin, as well as Pho-FAK in the implantation site (0.81?±?0.35; 0.72?±?0.24), showed a higher-level than that in the non-implantation site (0.59?±?0.26; 0.48?±?0.27) or the control group (0.38?±?0.19; 0.36?±?0.25) (p?<?.05). The decreased E-cadherin and increased β1 integrin are implicated in tubal pregnancy. The involvement of β1 integrin maybe depends on β1 integrin/FAK signaling.     

Does methotrexate treatment for ectopic pregnancy influence the patient's performance during a subsequent in vitro fertilization/embryo transfer cycle?

In a study on the influence of methotrexate (MTX) treatment on ovarian stimulation characteristics during the subsequent IVF cycle, 14 patients admitted to our department with the diagnosis of ectopic pregnancy and successfully treated with MTX were evaluated. No differences were observed in ovarian stimulation characteristics between the IVF cycle that had resulted in the ectopic pregnancy and the IVF cycle that followed MTX treatment. Treating ectopic pregnancy with MTX has no influence on patients' performance in the following IVF cycle.