Infertility Following Retained Products of Conception: Does the Timing of Surgical Intervention Matter?

BACKGROUND: Despite the large volume of evidence on the management of retained products of conception (RPOC), there are virtually no data regarding the optimal time frame of surgical intervention in case of RPOC. OBJECTIVES: To examine whether the time interval between spontaneous vaginal delivery or pregnancy termination and the uterine evacuation due to pathologically confirmed RPOC influences the reproductive outcome. METHODS: We retrospectively reviewed all the records of women who were admitted to our department due to pathologically confirmed RPOC following either spontaneous vaginal delivery or pregnancy termination between January 2000 and December 2010. Based on the median time from delivery or pregnancy termination until the operative intervention in the study group, patients were stratified into two groups: early intervention (< 3 weeks) and late intervention (> 3 weeks). Reproductive outcomes were compared between the two study groups. RESULTS: Reproductive outcomes were analyzed in 172 patients with pathologically confirmed RPOC. Of them, 95 (55.2%) were included in the early intervention group and 77 (44.8%) in the late intervention group. There were no significant differences in the conception rate, mean time to conception, and the occurrence rate of a new infertility problem in women with early surgical intervention compared to those with late surgical intervention (P > 0.05). Furthermore, there was no significant difference between the groups in the pregnancy outcomes following RPOC. CONCLUSIONS: Early surgical intervention in women with pathologically confirmed RPOC following spontaneous vaginal delivery or pregnancy termination yields the same reproductive outcomes as late surgical intervention.

Comparison of Reproductive Outcomes following Retained Products of Conception after Vaginal Delivery versus First-Trimester Abortion.

OBJECTIVE: To compare the reproductive outcomes of women with pathologically confirmed retained products of conception (RPOC) following spontaneous vaginal delivery versus first-trimester pregnancy termination. METHODS: We retrospectively reviewed all cases of women who underwent uterine re-evacuation due to pathologically confirmed RPOC between January 1, 2000 and December 31, 2010. Reproductive outcomes were compared between women with RPOC following spontaneous vaginal delivery and those who underwent dilatation and curettage (D&C) due to first-trimester abortion. RESULTS: The study group consisted of 176 patients with pathologically confirmed RPOC. Of those, 83 (47.1%) were admitted after spontaneous vaginal delivery and 93 (52.9%) following D&C due to first-trimester abortion. There were no significant differences in the conception rate, the mean time to conception and the rate of a new infertility problem between women with RPOC after vaginal delivery compared to those following pregnancy termination (p > 0.05). Furthermore, there were no significant differences between the groups in pregnancy outcomes following RPOC. CONCLUSION: Pathologically confirmed RPOC harbors the same reproductive outcomes following spontaneous vaginal delivery and first-trimester pregnancy termination.

Integration of PET/CT into the preoperative evaluation of patients with early cervical cancer does not decrease the proportion of patients with positive lymph nodes found after surgery.

PURPOSE: The aim of this study was to evaluate whether preoperative positron emission tomography/computed tomography (PET/CT) in patients with early-stage cervical carcinoma reduced the proportion of patients with metastatic lymph nodes identified after surgery. PATIENTS AND METHODS: This is a multicenter case-control study of 599 patients with early cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy at 1 of 10 gynecological oncology units in Israel. The patients were divided into 2 groups according to whether or not they underwent a preoperative PET/CT. The primary outcome was the proportion of patients with nodal involvement. The 2 groups were compared with regard to the clinical and histological variables. RESULTS: Of the 599 patients who underwent surgery, 180 (36%) had preoperative PET/CT study. There were no significant differences between the PET/CT and control groups with regard to clinical and histological risk factors. The proportion of patients with involved nodes was similar in the control and PET/CT groups (20.8% vs 19%; P = 0.73) as well as the proportion of patients receiving adjuvant radiotherapy/chemoradiation (58.3% vs 55.1%; P = 0.55). CONCLUSIONS: Preoperative PET/CT in patients with early cervical cancer does not reduce proportion of patients with metastatic nodal involvement and the employment of multimodality treatment. Prospective clinical trials comparing management based on PET/CT findings are warranted.

Intercoat (Oxiplex/AP gel) for preventing intrauterine adhesions after operative hysteroscopy for suspected retained products of conception: double-blind, prospective, randomized pilot study.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of Oxiplex/AP gel (Intercoat) in reducing intrauterine adhesion formation after hysteroscopic treatment because of retained products of conception (RPOC). DESIGN: Prospective double-blind, randomized, controlled pilot study (Canadian Task Force classification I). SETTING: Tertiary medical center. PATIENTS: All women who underwent hysteroscopic treatment because of RPOC at our institution between September 2009 and June 2012 were invited to participate. After operative hysteroscopy, participants were randomized to either have their uterine cavity filled with Oxiplex/AP gel (study group, n = 26) or not (control group, n = 26). INTERVENTIONS: Diagnostic office hysteroscopy to assess for adhesion formation was performed after 6 to 8 weeks. Findings were graded according to the American Fertility Society classification. Rates of subsequent pregnancy in the 2 groups were assessed. MEASUREMENTS AND MAIN RESULTS: Intraoperative complication rates were similar between the 2 groups. There were no postoperative complications after Oxiplex/AP gel application. Moderate to severe adhesions developed in 1 woman (4%) in the study group and 3 (14%) in the control group (p = .80). During follow-up of 20 months (range, 2-33 months), 7 women (27%) in the treatment group conceived, compared with 3 (14%) in the control group (p = .50). CONCLUSION: Intrauterine application of Oxiplex/AP gel after hysteroscopic removal of RPOC is safe. In this small sample, the difference in the rate of intrauterine adhesions was not statistically significant. A larger study would enable further establishment of the safety and efficacy of use of this gel.

Coagulopathy associated with dilation and evacuation for second-trimester abortion.

OBJECTIVE: To characterize the clinical and laboratory features of coagulopathy following second-trimester surgical abortions. DESIGN. Retrospective study. SETTING: Gynecologic unit of a university-affiliated medical center. POPULATION: 1249 consecutive women underwent late second-trimester (16-24 weeks) surgical abortions between January 2002 and June 2010. Of those, 20 women (1.6%) were diagnosed with excessive bleeding accompanied by coagulopathy. METHODS: Women were divided into two groups based on whether the abortion was performed for fetal demise (n=14) or pregnancy termination (n=6). MAIN OUTCOME MEASURES: Gestational age, indication for abortion, blood clotting tests, number of blood products and coagulation factors administered. RESULTS: Women who had pregnancy termination began to bleed significantly earlier than those with fetal demise (p<0.05). A significantly higher number of women with fetal demise had a gradual deterioration of the clotting test, compared with women who had pregnancy termination (p<0.05). In women with fetal demise, early bleeding was associated with a more severe clinical presentation. CONCLUSIONS: Coagulopathy following surgical abortion manifests differentially in women who have fetal demise and those who have pregnancy termination, implying a different pathophysiology. Women with fetal demise suffering from excessive bleeding following surgical abortion accompanied with mild clotting test abnormalities should be carefully monitored to diagnose and treat an impending disseminated intravascular coagulation.

Fertility performance and obstetric outcomes among women with previous cesarean scar pregnancy.

OBJECTIVES: The purpose of this study was to assess fertility performance and obstetric outcomes after treatment of cesarean scar pregnancy. METHODS: We conducted a retrospective study in a large tertiary hospital in Israel. The study included 18 women with a diagnosis of cesarean scar pregnancy between 2000 and 2009. RESULTS: The incidence of cesarean scar pregnancy among our parturient patients was 1 per 3000 for the general obstetric population and 1 per 531 among those with at least 1 cesarean delivery. Sixteen were treated primarily with methotrexate. Two were treated primarily by surgery, and 2 more were treated by surgery after failed methotrexate treatment. After cesarean scar pregnancy treatment, 7 women conceived spontaneously, and 1 conceived by in vitro fertilization-intracytoplasmic sperm injection. The remaining 10 (55%) did not wish to conceive again. Two of the women who became pregnant (25%) had recurrent cesarean scar pregnancy. CONCLUSIONS: This study shows encouraging results for fertility performance and obstetric outcomes after treatment of cesarean scar pregnancy. Nevertheless, the risk of recurrent cesarean scar pregnancy is not negligible.

Does intraoperative spillage of benign ovarian mucinous cystadenoma increase its recurrence rate?

OBJECTIVE: To report a higher than estimated recurrence rate of benign mucinous cystadenomas after complete resection of the first one, and to assess potential risk factors for recurrence after complete surgical excision. STUDY DESIGN: We retrospectively reviewed all cases of women who underwent either laparoscopic or laparotomic removal of benign mucinous adnexal cysts by either adnexectomy or cystectomy in our institution between 1996 and 2006. RESULTS: Included were the data of 42 women who fulfilled study entry criteria. Three of them (7.1%) underwent a second operation because of a recurrence of the lesion. A significantly higher rate of women who had cyst recurrence had undergone cystectomy as opposed to adnexectomy (P < .05). Intraoperative rupture of cysts during cystectomy was also significantly associated with cyst recurrence (P < .03). CONCLUSION: Mucinous cystadenoma recurrence is apparently not as rare as reported in the literature. Intraoperative cyst rupture and cystectomy instead of adnexectomy emerged as being two risk factors for recurrence.

Inadvertent rupture of benign cystic teratoma does not impair future fertility.

OBJECTIVE: We sought to investigate the reproductive outcomes of women who underwent laparoscopic removal of benign cystic teratoma with or without intraoperative spillage. STUDY DESIGN: The reproductive outcomes of reproductive age women following laparoscopic removal of benign cystic teratoma from 1997 through 2007 were investigated by a telephone questionnaire. RESULTS: In all, 128 reproductive age women underwent benign cystic teratoma removal, and reproductive outcomes were available for 45. Among those 45 women, intraoperative spillage occurred in 16 (35.6%). The rate of spontaneous pregnancies was significantly lower for the nonspillage compared to the intraoperative spillage groups (20/29 [68.9%] vs 16/16 [100%], respectively; P = .01). However, the median time from surgery to the first pregnancy was similar (22 and 18.5 months, respectively; P = .9). From the 9 remaining women in the nonspillage group, 4 conceived with ovulation induction, 2 conceived with in vitro fertilization, and 3 were infertile. CONCLUSION: Intraoperative spillage of benign cystic teratomas does not lead to long-term infertility.

Laparoscopic removal of adnexal cysts: is it possible to decrease inadvertent intraoperative rupture rate?

OBJECTIVE: The objective of the study was to characterize surgical risks for intraoperative rupture of benign adnexal lesions during laparoscopy. STUDY DESIGN: We conducted a retrospective review of cases of laparoscopic removal of ovarian cysts (adnexectomy or cystectomy) in our institution from 2002-2006, excluding procedures in which cysts were intentionally ruptured. RESULTS: There were 256 operations (263 ovarian cysts). The patients' mean age was 40.9 +/- 15.8 years. The overall rate of inadvertent intraoperative rupture of cyst was 16.6% (adnexectomies 7.4% and conservative cystectomies 29.5%; P < .001). There was no significant correlation between inadvertent intraoperative rupture and adnexal torsion, pelvic adhesions, bilateral adnexal surgery, concomitant uterine surgery, presence of pelvic endometriotic foci, pregnancy, and surgeons' experience. Only cyst size and cystectomy procedure were positively and significantly associated with inadvertent cyst rupture (multivariate regression analysis). CONCLUSION: Inadvertent intralaparoscopic rupture of adnexal cyst is significantly associated with cystectomies of large ovarian cysts for which laparotomy or laparoscopic-assisted extracorporeal cystectomy should be considered.

Safety of late second-trimester pregnancy termination by laminaria dilatation and evacuation in patients with previous multiple cesarean sections.

OBJECTIVE: To assess whether there is an increased perioperative risk in termination of late second-trimester pregnancy after multiple cesarean sections by laminaria dilatation and evacuation. STUDY DESIGN: During the period between January 2002 and June 2008, 636 consecutive patients underwent late second-trimester (17-24 weeks) pregnancy terminations by dilatation and evacuation. Patients were divided into 3 subgroups: those with no previous cesarean section (n = 545), those with 1 previous cesarean section (n = 59), and those with several previous cesarean sections (n = 32). RESULTS: There were no significant differences in major perioperative complications, such as anesthetic complications, need for blood transfusion, and cervical lacerations comparing the 3 subgroups. Importantly, there were neither cases of uterine perforation nor retained products of conception in the 3 subgroups. CONCLUSION: Late second-trimester pregnancy termination after multiple cesarean sections by laminaria dilatation and evacuation is probably not associated with an increased perioperative risk. Larger studies are needed to empower this study.

The safety of conception occurring shortly after methotrexate treatment of an ectopic pregnancy.

The objective of this study was to determine whether a single or repeated injection of methotrexate (MTX) to treat ectopic pregnancy results in either teratogenicity or other bad obstetric outcome in the pregnancy that shortly follows treatment. Data were retrieved from the medical records of 314 women treated with MTX for ectopic pregnancy in our institute (2000-2006) included age, MTX dosage, interval between last MTX treatment to conception, results of ultrasonographic follow-up of the subsequent pregnancy, triple test, karyotype testing, pregnancy outcome, and newborn weight and Apgar score. A logistic regression model based on pregnancy outcome as the dependent variable and interval since last MTX treatment as the independent variable estimated the odds ratio for the safety of conception occurring shortly after the treatment. Complete information was obtained for 125 pregnancies. Forty-five pregnancies occurred within 6 months (mean 3.6+/-1.7) after the last MTX treatment. The outcome of these pregnancies was compared with that of 80 pregnancies which occurred > or =6 months (mean 23.6+/-14.7) after the last MTX treatment. The fetal malformation and adverse outcome rates for both groups were similar (odds ratio 1.003, 95% CI 0.98-1.02). According to a logistic regression analysis, the interval between the last MTX treatment for ectopic pregnancy had no effect on the outcome of the pregnancy that shortly followed it. The results of this study support the notion that conceiving within the first 6 months after treatment with MTX for ectopic pregnancy is safe and not associated with any increase in the examined adverse pregnancy outcome parameters.

A comparison of perioperative morbidity, perioperative mortality, and disease-specific survival in elderly women (>or=70 years) versus younger women (<70 years) with endometrioid endometrial cancer.

OBJECTIVE: The study compares the perioperative morbidity and mortality rates of elderly (>or=70 years) and younger (<70 years) patients with endometrioid endometrial cancer. METHODS: The study cohort consisted of 115 consecutive women undergoing explorative laparotomy because of endometrioid endometrial cancer. Clinical data included patients' age, comorbidities, chronic use of medications, body mass index (kg/m), previous surgical procedures, surgical International Federation of Gynecology and Obstetrics stage, histological grade, relevant prognostic factors, a number of dissected lymph nodes, occurrence of perioperative complications, postoperative hospital stay (in days), and long-term disease-specific survival (in months). RESULTS: Patients were divided into 2 groups: those younger than 70 years (group 1: 84 women, 73%) and those 70 years or older (group 2: 31 women, 27%). Although, as expected, elderly women had more major comorbidities, the rate of perioperative complications was similar between the 2 groups. In a logistic regression model, only chronic lung disease, gastrointestinal disease, and past abdominal surgery correlated with a higher rate of perioperative complications. None of the cohort patients died during the perioperative period. The long-term disease-specific survival was significantly poorer for the older group. CONCLUSION: Chronological age by itself should not be a contraindication for the proper surgical treatment of elderly women with endometrioid endometrial cancer, because it is a poor predicting factor for perioperative morbidity and mortality.

Paraovarian cysts of neoplastic origin are underreported.

INTRODUCTION: We suspected that paraovarian cysts of neoplastic origin may be underreported. This study was designed to evaluate our data on the pathologic characteristics of cystic lesions located in the paraovarian area and compare them with previous studies that claimed the vast majority of these lesions were simple paraovarian cysts and only few (1.69% to 5%) were neoplastic ones. METHODS: This is a retrospective analysis of the clinical, surgical, ultrasonographic, and pathologic features of 59 women operated on for cystic paraovarian lesions at our institution from January 2002 to April 2006. RESULTS: Forty-four women (74.6%) had simple paraovarian cysts, and 15 (25.4%) had benign neoplastic paraovarian cysts (7 cystadenomas and 8 cystadenofibromas). There were no cases of malignant tumor. There was no difference in the clinical presentation of the women with either type of cyst. Preoperative ultrasound examinations (n=50) demonstrated more complex cysts with internal papillary projections in the group with neoplastic paraovarian cysts (41.7% compared with 7.9%, P=0.01). The macroscopic pathologic examinations revealed a significantly increased percentage of gross papillary excrescences in the group of neoplastic paraovarian cysts (10/15, 66.7%) compared with the group with simple paraovarian cysts (3/44, 6.8%, P<0.01). Other pathologic features did not differ between the 2 study groups. DISCUSSION: Our analysis revealed a higher percentage of paraovarian cysts of neoplastic origin ( approximately 25%) than the figures quoted in most previous reports. CONCLUSION: Intraoperative inspection for diagnosing the cyst type and more frequent use of endobag devices to avoid spillage of cystic fluid are recommended.

Can we rely on blind endometrial biopsy for detection of focal intrauterine pathology?

OBJECTIVE: To compare the diagnostic power of random endometrial biopsy with hysteroscopy for intrauterine lesions. STUDY DESIGN: A retrospective cohort study of 639 women evaluated by diagnostic office hysteroscopy and endometrial biopsy (Novak curette) was carried out between 10/1997-6/2000. Reasons for evaluation were postmenopausal bleeding, abnormal uterine bleeding, ultrasound or hystero-salpingography findings, intrauterine device removal, suspected retained products of conception, infertility, late abortions and recurrent abortions. RESULTS: The women's mean age was 43.4+/-13.3 years (range, 18-88). The most prevalent indication for investigation was abnormal uterine bleeding (n=218, 34.1%), followed by sonographic or hystero-salpingographic findings (n=167, 26.1%). Hysteroscopy revealed a normal uterine cavity in 367 (57.4%) women. Endometrial polyps and submucosal fibroids were the most common hysteroscopic findings (in 151 [23.6%] and 72 [11.3%], respectively). The hysteroscopic findings were compared with the pathology results in 558 cases. The sensitivity of the Novak curette for detection of endometrial polyps and submucosal fibroids was only 8.4% and 1.4%, respectively. The positive predictive value (30.9%) and the negative predictive value (57.9%) for both lesions were likewise low. On the other hand, hysteroscopy was not effective in diagnosing the 27 cases of hyperplasia (26 simple and one complex) all without atypia. CONCLUSION: Random endometrial sampling alone is not effective for diagnosing focal lesions of the uterine cavity and should be combined with other modalities, preferably diagnostic hysteroscopy.

Predictors of tuboovarian abscess in acute pelvic inflammatory disease.

OBJECTIVE: To define the predictors discriminating between patients developing tuboovarian abscess (TOA) and those with non-TOA acute pelvic inflammatory disease (PID) on the day of admission to the hospital. STUDY DESIGN: One hundred sixty-three patients were evaluated and divided into 2 groups: 42 patients diagnosed with clinical and sonographic evidence of TOA and 121 diagnosed with PID. Relying upon the significant differences between the 2 groups, cutoff levels yielding the best degree of discrimination were determined. RESULTS: A palpable adnexal mass in a woman older than 42 years and erythrocyte sedimentation rate > 50 mm/h were the best predictors of TOA. There was no difference in the mean temperature or number of sick days prior to hospitalization. CONCLUSION: Our results suggest that there are parameters that can be used as predictors of TOA and prolonged hospital stay. These parameters can advance the beginning of more aggressive antibiotic treatment.

Combined local and systemic methotrexate treatment of viable ectopic pregnancy: outcomes of 31 cases.

PURPOSE: Medical treatment of viable unruptured ectopic pregnancies by systemic methotrexate (MTX) is controversial due to elevated failure rates. This study describes a combined local and systemic MTX administration and compares the outcomes between viable ectopics in different locations. METHODS: This retrospective study evaluated 31 patients treated with combined local (sonographically guided) and systemic MTX for viable, unruptured ectopic pregnancies. Success was defined by pregnancy resolution without surgical intervention. Details on subsequent pregnancies were obtained via telephone questionnaires. RESULTS: The ectopic pregnancies were located in the fallopian tube (n = 23), cesarean section scar (n = 5), and intramural portion of the tube (interstitial pregnancy) (n = 3). beta-Human chorionic gonadotropin levels and gestational weeks were similar. The combined treatment was successful in 73.9%, 100%, and 66.7% of cases, respectively (p > 0.05). Details regarding reproductive outcomes were available for 28 women (90.3%). Eighteen of the 24 women attempting to conceive became pregnant, and 15 of these had at least one live birth. There were three subsequent tubal pregnancies, all in patients with previous tubal pregnancies. CONCLUSION: Combined MTX administration is effective and safe for treating viable cesarean scar pregnancies but is less successful for viable tubal or interstitial pregnancies. Reproductive outcomes following the combined MTX treatment are comparable to other treatment modalities for ectopic pregnancy.

[Adnexal masses: understanding and management].

Asymptomatic adnexal masses have become common findings due to the widespread use of the transvaginal ultrasound. Most asymptomatic adnexal masses are benign, but malignancy should still be excluded. The assessment of women with adnexal masses, intended to detect the ones suspicious for malignancy, includes the medical history, physical examination, ultrasound scan with Doppler flows, and, in some cases, the CA-125 levels. Once the patient has completed the primary assessment, the important decision is whether to follow her conservatively (if a benign condition is probable), or to proceed to surgery (if malignancy is suspected). This review discusses the evaluation, differential diagnosis, and general approach to adnexal masses, and proposes a management flow chart.

Torsion of normal adnexa in postmenarchal women and risk of recurrence.

OBJECTIVE: To compare the incidence of recurrent torsion of normal adnexa to recurrent torsion of abnormal adnexa in postmenarchal women. METHODS: All cases of surgically confirmed adnexal torsion operated on in our department from January 2002 to April 2006 were retrospectively analyzed. Classification as torsion of pathologic adnexa versus torsion of normal adnexa was based on pre- and postoperative pelvic sonograms, operative findings, and pathologic diagnoses (when available). The torsion recurrence rates were evaluated by a telephone questionnaire, with 90.5% compliance. RESULTS: Twelve women had twisted normal adnexa and 50 women had twisted abnormal adnexa. The women with twisted normal adnexa were younger (25.5+/-7.9 years versus 31.4+/-11.4 years, P=.10) and had a lower median parity (0 versus 1, P=.06). Both groups had similar clinical presentations and a similar mean time from admission to surgery. The torsion recurrence rates were 63.6% (95% confidence interval [CI] 0.3-0.9) in the twisted normal adnexa group and 8.7% (95% CI 0.02-0.2) in the twisted abnormal adnexa group (P<.001). The retorsion risk of the pathologic adnexa was especially low after cystectomy (5.3%, 95% CI 0.001-0.3) or salpingo-oophorectomy (0%). The Kaplan-Meier life table analysis also showed a higher retorsion risk for normal adnexa (P=.008). CONCLUSION: The current adnexa-sparing laparoscopic management of adnexal torsion by simply untwisting may predispose to recurrent torsion of normal adnexa. The role of ovariopexy procedures in the prevention of recurrent torsion events remains uncertain. LEVEL OF EVIDENCE: III.

Arteriovenous malformation after uterine curettage: a report of 3 cases.

BACKGROUND: Acquired uterine arteriovenous malformation is a rare but potentially life threatening condition and, as such, must be considered in the differential diagnosis of cases of abrupt, profuse vaginal bleeding following uterine curettage. The condition can easily be confused with retained products of conception and gestational trophoblastic disease. CASES: One case was managed surgically, while 2 others were treated with selective embolization. CONCLUSION: A positive medical history, the clinical presentation and features for the the ultrasonic appearance are the main features for the correct differential diagnosis and treatment of traumatic arteriovenous malformation resulting from uterine curettage.

Outcomes of conception subsequent to methotrexate treatment for an unruptured ectopic pregnancy.

OBJECTIVE: To assess the risk of adverse pregnancy outcomes in subsequent pregnancies among women treated with methotrexate for ectopic pregnancy. METHODS: In a retrospective single-center study, data were assessed for women treated with methotrexate for ectopic pregnancy at Asaf Harofe Medical Center, Zerifin, Israel, between May 2004 and May 2014. RESULTS: Overall, 226 women were treated with methotrexate for ectopic pregnancy and subsequently conceived. The median time from treatment to conception was 10 months (range 1-120 months), and 127 women conceived within 12 months of treatment. Except for early missed abortion-which affected 23 (10.2%) pregnancies-adverse pregnancy outcomes such as fetal malformations were rare. The frequency of early abortion was lowest for women who conceived within 6 months of treatment with methotrexate (3/93, 3.2%), increased between 6 and 23 months (15/83, 18.1%), and remained high thereafter (7/50, 14.0%; P=0.006). CONCLUSION: The frequency of fetal malformation in a subsequent pregnancy was low among women treated with methotrexate for ectopic pregnancy. The frequency of early missed abortion was lowest during the first 6 months after treatment with methotrexate.