Outcome of pregnancies occurring within 1 year of hydatidiform mole.

OBJECTIVE: To determine the outcome of subsequent pregnancies in patients with partial or complete molar pregnancy who conceive before completing the recommended hCG follow-up of at least 6 months. METHODS: Retrospective record review of patients with partial or complete mole who conceived before the standard gonadotropin follow-up of 6 months was completed during 1980-1998. RESULTS: Sixty-seven patients with molar pregnancy who conceived before completion of hCG follow-up were identified. Thirty-five (52.2%) patients had a prior partial mole, and 32 (47.8%) had a prior complete mole. The mean interval from first achieving undetectable hCG level to new pregnancy was 3.1 and 3.4 months in patients with partial and complete mole, respectively. Eleven patients underwent elective termination, and 12 were lost to follow-up. Of the remaining 44 patients, 33 (75.0%) had live births, 10 had spontaneous abortions, and one had an ectopic pregnancy. A viable pregnancy outcome was achieved in 20 (83.3%) of 24 patients with partial mole and 13 (65.0%) of 20 patients with complete mole. None of the patients developed any evidence of postmolar persistent gestational trophoblastic tumor. None of the live births had any detectable fetal anomalies. CONCLUSION: The risk of persistent tumor is low and reproductive outcome is favorable once undetectable hCG levels are achieved. Pregnancies occurring before the completion of recommended hCG follow-up may be allowed to continue under careful surveillance.     

Outcome of Pregnancies Occurring before Completion of Human Chorionic Gonadotropin Follow-Up in Patients with Persistent Gestational Trophoblastic Tumor

OBJECTIVE: To determine the outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients treated with chemotherapy for gestational trophoblastic tumor. METHODS: Retrospective record review of patients with gestational trophoblastic tumor who conceived before standard hCG follow-up was completed during 1973-1998. RESULTS: Forty-three patients treated for gestational trophoblastic tumors conceived before human chorionic gonadotropin follow-up was completed. The antecedent pregnancy was complete mole in 31 (72.1%) and partial mole in 12 (27. 9%) patients. Of the 43 patients, 39 (90.7%) had stage I, 1 had stage II, and 3 had stage III disease. The mean interval from human chorionic gonadotropin remission to new pregnancy was 6.3 months (range 1-11 months). Ten patients underwent elective termination and four patients were lost to follow-up. Of the remaining 29 patients, 22 (75.9%) had term live births, 3 (10.3%) had preterm delivery, 3 had spontaneous abortion, and 1 (3.5%) had a repeat mole. Two cases of fetal anomalies were detected; one was inherited polydactyly and the other was hydronephrosis. One patient developed choriocarcinoma with lung involvement and underwent cesarean section at 28 weeks; a normal fetus was delivered and no choriocarcinoma was detected in the placenta. CONCLUSION: Pregnancies occurring in patients treated for gestational trophoblastic tumor before standard human chorionic gonadotropin follow-up is completed may continue under close clinical surveillance since the majority have a favorable outcome. However, patients should also be advised of the low but important risk of delayed diagnosis in case tumor relapse develops during early subsequent pregnancy.     

Repetitive hydatidiform mole with different male partners.

OBJECTIVE: The aim of this study was to determine the role of parental factors that may relate to the pathogenesis of molar pregnancy. METHODS: A retrospective review of six patients who had a molar pregnancy with at least two different partners at New England Trophoblastic Disease Center between 1965 and March 1999 was performed. RESULTS: A total of 34 pregnancies with 20 different partners were observed in 6 patients. These pregnancies resulted in 15 (44.1%) hydatidiform moles, 8 (23.5%) term live births, 7 (20.6%) therapeutic abortions, 3 (8.8%) spontaneous abortions, and 1 preterm delivery. While 5 patients had a molar pregnancy with 2 different partners, 1 patient had a molar pregnancy with 3 different partners. Two patients developed persistent postmolar gestational trophoblastic tumor in 3 (20.0%) of the 15 episodes of molar pregnancy. Three of the male partners reported a total of 7 healthy children from prior relationships. CONCLUSION: The experience in these six patients suggests that a primary oocyte problem may contribute to the development of molar pregnancy.     

Return of fertility after successful chemotherapy treatment of gestational trophoblastic tumors.

OBJECTIVE: To determine the effect of chemotherapy on patients who wished to conceive after successful treatment of gestational trophoblastic disease. Patients-During a 12-year period (1984-1995), 90 patients with gestational trophoblastic tumor at Jordan University Hospital received repeated courses of chemotherapy; 85 patients are in continued remission (42 invasive mole and 43 choriocarcinoma). Fifty-five patients wished to conceive. Main outcome measures-Pregnancy, live births. RESULTS: Forty-two patients (76%) achieved pregnancy, resulting in 20 pregnancies and 94 viable babies. CONCLUSIONS: Chemotherapy is very effective in the cure of gestational trophoblastic tumors. Return of fertility compares favorably with the general population of the same reproductive age. There appears to be no increase in fetal congenital malformations.     

Subsequent pregnancy experience in patients with molar pregnancy and gestational trophoblastic tumor

Modern therapy for molar pregnancy and gestational trophoblastic tumors has resulted in high cure rates and preservation of fertility, even in the setting of metastatic disease requiring chemotherapy. Patients and their partners facing future pregnancy after treatment for gestational trophoblastic disease express fear related to risk of disease recurrence and outcome of subsequent pregnancies. Data from the New England Trophoblastic Disease Center on later pregnancies following complete and partial mole as well as persistent gestational trophoblastic tumor show that patients, in general, can anticipate normal subsequent pregnancy outcomes.     

Analysis of pregnancy outcome after chemotherapy of trophoblastic disease

The pregnancy outcome of 57 women who had been treated for trophoblastic disease, between 1975 and 1982, was studied. All patients had regular menstrual cycle within six months after the last chemotherapy. Frequency of secondary infertility is 5% (3/60). No correlation between the amount of chemotherapy and secondary infertility was apparent. Of eighty-three pregnancies in 57 women, 55 pregnancies or 66.3% terminated in full term deliveries, 4 or 4.8% terminated in premature deliveries. Eleven of the 83 or 11.3% ended in spontaneous abortions and 2 or 2.4% in recurrent hydatiditorm mole. Only one infant (1.7%) had congenital malformation. There was no increase in fetal wastage or congenital anomaly when compared with pregnancies prior to chemotherapy or after untreated molar patients. Among the 59 live born infants, 4 or 6.8% infants belong to light for date, 49 or 83.1% to appropriate for date and 6 or 10.2% to heavy for date. Chemotherapic agents, mainly MTX and Act-D, appeared to have no effect on fetal growth. The incidence of choriocarcinoma subsequent to pregnancy in treated patients was 1.8% (1/57) and was 0.6% (2/365) in untreated molar patients (n.s.).     

Primary microsurgery for postinflammatory tubal infertility

Pelvic inflammatory disease is a common cause of tubal infertility. The pregnancy outcomes in 161 patients who underwent primary microsurgical tuboplasty for postinflammatory tubal disease at the Mayo Clinic from 1977 through 1981 were evaluated. The outcome (3-year rate) was evaluated for each category of microsurgical procedures. The proximal anastomosis group had a conception rate of 71% (50% live births, 30% spontaneous abortions, 6% ectopic pregnancies). The terminal salpingoneostomy group, which accounted for the largest number of procedures, had a conception rate of 47% (32% live births, 12% spontaneous abortions, 11% ectopic pregnancies). Even after microsurgical tubal reconstruction, most women do not achieve a live birth. Pregnancy outcome is probably related to several factors reflecting the severity of pre-existing intrinsic damage. Prognostic factors that may better predict pregnancy outcome are discussed.     

Hysteroscopic treatment of uterine septum

Authors report their 4 years experience in the treatment of uterine septum by hysteroscopic metroplasty. 35 patients underwent procedure; no complications occurred. Postoperative reproductive outcome was evaluated in 29 women with follow-up longer than 6 months. Patients were divided into 2 groups according to presence or absence of associated factors compromising fertility. Group A composed of 19 women in which uterine septum was the only cause of pregnancy wastage. Preoperatively they had 40 pregnancies all ending in spontaneous abortion. Postoperatively 15 (79%) patients conceived and 13 (68%) had a live baby. Totally they had 18 pregnancies, 2 (12%) ended in abortion, 1 in molar pregnancy, 1 in premature delivery, 11 delivered at term and 3 are currently beyond 20 weeks pregnant, for a live birth rate of 78%. Life table analysis showed an estimated pregnancy rate of 82% at 12 months, monthly fecundability was 0.13. Group B composed of 10 women in which other factors compromising fertility were present. Preoperatively only 5 experienced pregnancy. Totally they had 8 pregnancies 7 (86%) of which ended in abortions and one in extrauterine pregnancy. Postoperatively only 3 (30%) had pregnancy and all had a live baby. Totally they had 4 pregnancies, 1 ended in abortion and 3 at term for a live birth rate of 75%. Life table analysis showed an estimated pregnancy rate of 11% at 12 months, monthly fecundability rate was 0.01. Hysteroscopic metroplasty proved to be safe and effective for solving pregnancy wastage caused by uterine septum. If other factors compromising fertility were present metroplasty did not increase fecundability, but improved live birth rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful term pregnancy after selective arterial embolization of symptomatic arteriovenous malformation in the setting of gestational trophoblastic tumor

BACKGROUND: Patients with arteriovenous malformations (AVMs) are at risk for significant vaginal hemorrhage, and are traditionally managed surgically. In the patient desiring future fertility, conservative management via selective arterial embolization is a reasonable option. Only a few cases have been previously reported of successful pregnancy after this procedure in the setting of gestational trophoblastic disease (GTD). CASE: A 31-year-old gravida 1 para 0 was treated for persistent gestational trophoblastic tumor after a complete mole in 1997. She presented with heavy vaginal bleeding, and arteriogram demonstrated a large uterine AVM. The patient underwent selective uterine artery embolization with complete resolution of bleeding, as well as arteriographic cessation of flow through the AVM. After two first-trimester spontaneous abortions, the patient successfully completed a normal pregnancy, resulting in the forceps-assisted delivery of a healthy female infant. CONCLUSION: Successful term pregnancy can occur after selective uterine artery embolization in women hemorrhaging from symptomatic GTD-associated AVM.     

Pregnancy outcome after exposure to the probiotic Lactobacillus in early pregnancy

The present study prospectively assessed pregnancy outcome of women taking probiotics during the periconceptional period. A group of 104 women who had taken Lactobacillus in early pregnancy and 200 age- and parity-matched control pregnant women exposed to non-teratogenic agents were also recruited into the study and followed-up prospectively. Median gestational age of women exposed to Lactobacillus was 5.2 (range: 1.9-17.6) weeks. Exposure was at a mean dose of 510 mg/day for a median of 4.0 days (range: 1-90 days). In the exposed group, pregnancy outcomes included 96 live births and eight spontaneous abortions versus 187 live births and 21 spontaneous abortions in the non-exposed group. There was no statistical difference in adverse pregnancy outcomes, including the number of spontaneous abortions, pre-term births as well as a low birth weight between the two groups (p > 0.05). In the exposed group, there were two (2.1%) major congenital malformations in comparison with five (2.7%) in the comparison group (p = 0.7). In conclusion, no association was identified between ingestion of Lactobacillus in early pregnancy for a limited period of time and adverse pregnancy outcomes. However, rare pregnancy outcomes may have been missed due to the limited sample size included in the study.     

Pregnancy outcomes in women with mechanical heart valves

OBJECTIVE: To evaluate maternal complications and perinatal outcomes in women with mechanical heart valves treated with warfarin and heparin during pregnancy. STUDY DESIGN: A retrospective chart review was performed on 45 pregnancies in 28 women who were previously fitted with mechanical valve prostheses and treated between 1991 and 2005 at Seoul National University Hospital. Outcome parameters were maternal complications and perinatal outcomes. RESULTS: Overall, there were 27 live births (60%), 7 stillbirths (15.6%), 2 therapeutic terminations in the second trimester (4.4%), 9 first-trimester spontaneous abortions (20%) and 2 neonatal deaths after preterm delivery. After excluding 9 first-trimester spontaneous abortions and 3 pregnancies administered warfarin throughout pregnancy, there were significantly more live births among patients administered heparin only after a diagnosis of pregnancy than among those administered warfarin from the second trimester (11 of 11 vs. 13 of 22, p = 0.015). One patient with mitral valve thrombosis during heparinization in the first trimester received valve replacement surgery and then aborted. Late postpartum hemorrhage occurred in 1 patient. All stillbirths and therapeutic terminations occurred in women being administered warfarin. CONCLUSION: Warfarin use from the second trimester in combination anticoagulation regimens increases the risk of an adverse perinatal outcome.     

Recurrent miscarriage associated with antiphospholipid antibodies: prophylactic treatment with low-dose aspirin and fish oil derivates

PROBLEM: The aim of this study was to evaluate the effects of two different prophylactic protocols, low-dose aspirin and fish oil derivates, in the treatment of patients with recurrent pregnancy loss associated with antiphospholipid antibodies (APA) syndrome. METHODS: A prospective study included 30 patients who were alternately assigned to treatment. Each patient had had at least two consecutive spontaneous abortions, positive antiphospholipid antibodies on two occasions, and a complete evaluation. RESULTS: Among patients treated with low-dose aspirin, 12 out of the 15 (80%) pregnancies ended in live births. In the fish oil derivate group 11 out of the 15 (73.3%) ended in live births (p > 0.05). There were no significant differences between the low-dose aspirin and the fish oil derivates groups with respect to gestational age at delivery (39.9 +/- 0.4 vs 39 +/- 1.5 weeks), fetal birth weight (3290 +/- 200g vs 3560 +/- 100 g), number of cesarean sections (25% vs 18%), or complications. CONCLUSION: There were no significant differences in terms of pregnancy outcome between women with recurrent pregnancy loss associated with APA syndrome treated with low-dose aspirin or fish oil derivates.     

Combination chemotherapy with 5-fluorouracil, methotrexate and etoposide for patients with high-risk gestational trophoblastic tumors: a report based on our 11-year clinical experiences

OBJECTIVES: To evaluate the efficacy, toxicity, and survival of patients with high-risk gestational trophoblastic tumors (GTTs) treated with the 5-fluorouracil (5-FU), methotrexate (MTX) and etoposide (VP-16) regimen. METHODS: Between 1992 and 2003, 26 consecutive patients with FIGO-defined high-risk GTTs were treated with 5-FU, MTX and VP-16 regimen. Among them, 9 patients had received prior chemotherapy. Remission rate, causes of treatment failure, and toxicity were analyzed retrospectively. RESULTS: After treatment with 5-FU, MTX and VP-16 regimen, 21 of 26 gained complete respond (80.8%). Two patients were performed adjuvant hysterectomy and both cured ultimately. Five developed resistance (19.2%), and 1 died of widespread metastases (3.8%). All 5 patients who developed resistance were treated with multidrug regimen of etoposide, methotrexate, and actionmycin D alternating with cyclophosphamide and vincristine (the EMA/CO); 4 were salvaged and 1 died of refractory disease. No ones relapsed. WHO grade 4 leukocytopenia and thrombocytopenia with the 5-FU, MTX and VP-16 regimen occurred in 9.0% and 2.4%, respectively, of the total 167 cycles; other toxic effects were acceptable and manageable. With mean follow up of 37 months, neither relapse nor secondary tumor was observed. CONCLUSIONS: According to our 11 years of clinical observation, 5-FU, MTX and VP-16 chemotherapy is one of effective multiagent regimen for patients with high-risk GTTs. Its toxicity is mild and manageable. For patients with high-risk and refractory GTTs, this new triple salvage chemotherapy regimen may be an effective alternative.     

Inappropriate management of women with persistent low hCG results

The USA hCG Reference Service is a consulting service with a specialized clinical laboratory aiding physicians in the interpretation of conflicting or nonrepresentative human chorionic gonadotropin (hCG) results. We have consulted on 189 cases with persistent low levels of hCG but no evidence of pregnancy or tumor. Quiescent gestational trophoblastic disease (GTD) was identified in 121 cases by the absence of invasive trophoblast antigen and nonresponse to chemotherapy (64 cases with a history of hydatidiform mole or gestational trophoblastic neoplasia (GTN) and 57 cases following antecedent pregnancy). Another 61 Reference Service cases hadfalse positive hCG, and we observed 7 cases with low levels of hCG of pituitary origin (hCG subsequently suppressed by estrogen-progesterone medication). Most disturbing is that the majority of these cases (68%) received needless therapy for assumed GTN/choriocarcinoma/placental site trophoblastic tumor before consultation with the Reference Service. One hundred twenty-eight of the 189 patients (77 of 121 with quiescent GTD, 48 of 61 withfalse positive hCG and 3 of 7 with pituitary hCG) underwent therapy ranging from single-agent chemotherapy (117 cases), to EMA-CO combination chemotherapy (etoposide, methotrexate, actinomycin D alternating with cyclophosphamide and vincristine) (16 cases), to hysterectomy and/or bilateral salpingo-oophorectomy (31 cases). False positive hCG and pituitary hCG would obviously not respond to these treatments, and no treated cases of quiescent GTD responded to chemotherapy orfully responded to hysterectomy. The continued needless treatment of patients with quiescent GTD, even after multiple publications, is entirely avoidable. Unfortunately, the number of needlessly treated cases referred to the Reference Service is increasing.     

Psychosocial and reproductive outcomes of gestational trophoblastic diseases

Current therapy for molar pregnancy and gestational trophoblastic neoplasias (GTNs) has resulted in high cure rates with preservation of fertility, even in the setting of chemotherapy for widespread metastatic disease. Data from the New England Trophoblastic Disease Center on later pregnancies following complete and partial mole, as well as persistent GTN show that patients can, in general, anticipate normal subsequent pregnancy outcome. Nevertheless, patients and their partners often express anxiety and fear related to the risk of disease recurrence and the outcome of subsequent pregnancies after treatment for gestational trophoblastic disease. These psychosocial sequelae may persist for years in both patients and their partners.     

Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study

OBJECTIVE: Bupropion was developed for the treatment of depression, but subsequently was found to be effective for smoking cessation. To date, there are no prospective comparative studies examining its safety in pregnancy. The primary objective was to determine whether bupropion increases the risks for major malformations above baseline. The secondary objective was to examine the rates of live births, stillbirths, spontaneous and therapeutic abortions, mean birth weight, and gestational age at birth. STUDY DESIGN: Women who were pregnant or planning a pregnancy and taking bupropion were enrolled in the study. Follow-up of pregnancy outcome was carried out between 4 months and 1 year after delivery. Three comparisons were carried out: 1) women exposed to bupropion vs a nonteratogen group; 2) those taking for depression vs other antidepressants, vs a nonteratogen group; 3) spontaneous abortions were compared between those taking for depression, vs another antidepressant group vs a nonteratogen group. RESULTS: We completed follow-up on 136 women exposed to bupropion during the first trimester of pregnancy. There were (105) live births, no major malformations, the mean birth weight was (3450g), the mean gestational age at delivery was (40 weeks), the number of spontaneous abortions was 20, there were 10 therapeutic abortions, there was 1 stillbirth, and 1 neonatal death. There were no statistically significant differences between any of the end points we examined between the exposed and comparison groups, with the exception of significantly more spontaneous abortions in the bupropion group (P = .009). CONCLUSION: These results suggest that bupropion does not increase the rates of major malformation above baseline. The higher rates of spontaneous abortions are similar to other studies examining the safety of antidepressants during pregnancy.     

Acute acetaminophen overdose during pregnancy

During a nationwide acetaminophen overdose study conducted at the Rocky Mountain Poison and Drug Center from 1976-1985, 113 patients entered into the study were reported to be pregnant at the time of the overdose. Follow-up, including appropriate laboratory and pregnancy outcome data, was available in 60 cases. Of these, 19 women overdosed during the first trimester, 22 during the second trimester, and 19 during the third trimester of pregnancy. Of the 24 patients with acetaminophen levels above the acetaminophen overdose nomogram line, ten were treated with N-acetylcysteine within 10 hours post-ingestion; eight delivered normal infants and two had elective abortions. Of ten patients treated with N-acetylcysteine 10-16 hours post-ingestion, five delivered viable infants, two had elective abortions, and three had spontaneous abortions. Of four women treated with N-acetylcysteine 16-24 hours post-ingestion, one mother died, and there was one spontaneous abortion, one stillbirth, one elective abortion, and one delivery. Multiple logistic regression demonstrated a statistically significant correlation between the time to loading dose of N-acetylcysteine and pregnancy outcome, with an increase in the incidence of spontaneous abortion or fetal death when treatment was begun late. We recommend that pregnant women who take an acetaminophen overdose and have a potentially toxic serum level be treated with N-acetylcysteine as early as possible.     

Clinicopathologic characteristics and subsequent pregnancy outcome in 139 complete hydatidiform moles

OBJECTIVE: The most common form of gestational trophoblastic disease is the complete hydatidiform mole (CHM). The study reports our experience of clinicopathologic characteristics and subsequent pregnancy outcome of patients with CHM. STUDY DESIGN: One hundred fifty-one subsequent cases with initial diagnosis of CHM were re-evaluated histopathologically. Clinical characteristics, the need for chemotherapy and subsequent pregnancy outcome were evaluated. RESULTS: Twelve out of 151 cases were re-evaluated as hydropic abortion, as partial hydatidiform moles or were insufficient for morphologic examination and therefore excluded from further analysis. The leading clinical symptoms of the remaining 139 cases were irregular vaginal bleeding (67%) and uterine enlargement (41%). Twenty-six patients (19%) required chemotherapy because of gestational trophoblastic neoplasia (GTN; low-risk: 23 out of 26). All patients were cured successfully. The subsequent pregnancy rate was 15% (21/139). Five patients suffered from abortions, 12 women delivered a healthy offspring. Four women presented with recurrent CHM with a spontaneous normalization of HCG levels after D&C. CONCLUSIONS: The clinical and morphologic diagnosis of CHM is a challenge, and diagnosis as well as treatment should be multidisciplinary and centralised. One fifth of CHM are at risk of a GTN, but the cure rate is 100% with adequate management. Pregnancy outcome following CHM is complicated by an increased risk of abortion.     

Reproductive outcomes after hydatiform mole and gestational trophoblastic neoplasia

Abstract

Gestational trophoblastic disease includes complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN). Given the very high-curability rate of trophoblastic disease, the risk of further molar pregnancy after CHM or PHM as well as the risk of second primary tumors and fertility compromise after chemotherapy for GTN represent major concerns. The incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or PHM, and is approximately 10% after two previous CHMs. Among patients who have received chemotherapy, there is an increased risk of myeloid leukemia which is mainly related to the cumulative dose of etoposide. Resumption of normal menses occurs in approximately 95% of women treated with chemotherapy, but menopause occurs 3 years earlier compared with those non-treated with chemotherapy. Term live birth rates higher than 70% without increased risk of congenital abnormalities have been reported in these women, and pregnancy outcomes are comparable to those of general population, except a slightly increased risk of stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is a therapeutic option reserved to highly selected, young women who do not present markedly enlarged uterus or diffuse multifocal disease within the uterus.     

Management of low-risk metastatic gestational trophoblastic tumors.

The clinical course of 48 patients with low-risk metastatic gestational trophoblastic tumors (GTTs) treated with primary single-agent chemotherapy was reviewed. All patients achieved sustained remission, although 25 (51%) required a second single-agent regimen, and 7 (14%) needed combination chemotherapy to achieve it. An average of 3.4 courses of chemotherapy were necessary to achieve remission, and 6 patients (12%) underwent resection of resistant tumor foci. Primary single-agent chemotherapy is a reasonable treatment option in patients with low-risk metastatic GTT.