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Clinical inquiries. How long is expectant management safe in first-trimester miscarriage?

More than 80% of women with a first-trimester spontaneous abortion have complete natural passage of tissue within 2 to 6 weeks with no higher complication rate than that from surgical intervention (strength of recommendation [SOR]: A, based on multiple randomized controlled trials [RCTs] and cohort studies). Expectant management is successful within 2 to 6 weeks without increased complications in 80% to 90% of women with first-trimester incomplete spontaneous abortion and 65% to 75% of women with first-trimester missed abortion or anembryonic gestation (presenting with spotting or bleeding and ultrasound evidence of fetal demise) (SOR: B, based on multiple cohort studies). There is no difference in short-term psychological outcomes between expectant and surgical management (SOR: B, based on RCT). Women experiencing spontaneous abortion with unstable vital signs, uncontrolled bleeding, or evidence of infection should be considered for surgical evacuation (SOR: C, expert opinion).

Abortion, Spontaneous↗

Fertility after discontinuation of oral contraceptives.

Concern has been expressed regarding fertility following oral contraceptive (Pill) use. A review of the literature indicates that there is a slight delay in the return of fertility in Pill users but no permanent impairment results. A small proportion of women experience a prolonged period of amenorrhoea following cessation of combined oral contraception, but whether the Pill plays an aetiological role is doubtful since there appear to be no differences in endocrine profiles amongst women with amenorrhoea following Pill use and those with secondary amenorrhoea who have never used oral contraceptives. Factors which may predispose to amenorrhoea following Pill use are: late onset of menarche, previous oligomenorrhoea and low body weight. Following adequate investigation and treatment, fertility rates in women with the so-called post-Pill amenorrhoea syndrome return to normal. There is no evidence of any delay in the return of fertility in women who use the progestogen-only Pill.

Abortion, Incomplete↗

Induction of abortion by vaginal administration of 15(s)15-methyl prostaglandin F2alpha methyl ester. A comparison of two delivery systems.

15-methyl PGF2alpha methyl ester in a slow releasing vaginal device was administered to 30 women in the first and second trimester of gestation. Ten women were early pregnant (31-49 days following the last menstrual period) and the remaining 20 patients in the 10th to 20th week of gestation. The first group received either a device containing 10 mg 0.5% 15-methyl PGF2alpha methyl ester or a half of that device and the second group either a 0.5% or 1% device. The results were compared with those found following repeated vaginal administration of triglycerides suppositories, containing 15-methyl PGF2alpha methyl ester, to 50 early pregnant patients and 30 patients in the second trimester of gestation. The mean total dose of the compound given to these two groups was 3.9 and 7.8 mg respectively. All the 60 early pregnant patients aborted following treatment judged from clinical course and decreasing HCG values. Bleeding started as a rule three to six hours following the start of treatment and continued for 10 to 14 days. In two patients the abortion was incomplete. The side effects in the patients who received half the 0.5% device was comparable to those following the repeated vaginal suppositories while in the patients who obtained the whole 0.5% device, the frequency of side effects was increased indicating that an unnecessary high dose was given. In all the three groups of patients in the late first and second trimester of pregnancy, treatment resulted in abortion within 24 hours in 90% of the patients. In the 1% device an accumulation of side effects was found during the first hours following the start of treatment probably due to an initial, more rapid absorption of 15-methyl PGF2alpha methyl ester. With the repeated administration and with the 0.5% device, the side effects occurred mainly in the hours prior to abortion. However, in all three groups of patients the side effects were within acceptable levels. These preliminary results indicate that further development on the device may result in an effective one vaginal administration treatment for termination of both first and second trimester pregnancies.

Abortion, Induced↗

Abortifacient effect and uterine cervix-dilating action of 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) in the form of a vaginal suppository (a randomized, double-blind, controlled study in the second trimester of pregnancy).

A newly synthesized 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) was clinically applied in the form of a vaginal suppository for therapeutic abortion of second trimester pregnancies. Its effects were studied in a double-blind test comparing it with an inactive placebo suppository. The study was conducted at 12 Japanese university hospitals. The number of patients was 125 in total, i.e. 63 receiving ONO 802 vaginal suppository (containing 1.0 mg ONO 802) and 62 receiving inactive placebo suppository. ONO 802 was more effective than placebo with a success rate of 87% (complete (71%) and incomplete (16%) abortions). The onset of uterine contractions was observed in 154.3+/-18.1 min. and the onset of uterine bleeding in 323.6+/-41.0 min. The expulsion of the fetus and placenta was observed in 955.4+/-97.0 and 961.6+/-97.0 min., respectively. The cervix dilating effect of ONO 802 was observed in 63.5% of the patients at 3 hours after the start of administration. Nausea, vomiting, abdominal cramps, diarrhea and pyrexia were noticed. However, all these side effects were transient and mild, requiring no treatment. No abnormality was observed in the puerperal course, duration of uterine bleeding or onset of subsequent menstruation following the therapeutic abortion. Therefore, the present study demonstrated that ONO 802 vaginal suppository was an effective and valuable drug for therapeutic abortion of second trimester pregnancies.

Abortifacient Agents↗

The effects of intramuscular injections of 15(S)-15-methyl prostaglandin F2alpha in failed abortions.

Intramuscular injections of 15(S)-15-methyl prostaglandin F2alpha (15-Me-PGF2alpha) induced abortion in 38 patients who had failed to abort with other techniques, such as intra-amniotic instillation of saline or PGF2alpha and intravaginal insertion of prostaglandin-impragnated Silastic devices. The intramuscular injections of 15-Me-PGF2alpha were initiated when the original abortion techniques, even when augmented by intravenous oxytocin, failed to produce expulsion of the fetus. The dose schedule was 250 microgram or 500 microgram every 2 to 4 hours, and the concomitant intravenous oxytocin was continued at a rate of 167 mU/minute. Of the 38 patients, 26 aborted with two or fewer injections of 15-Me-PGF2alpha, and 30 patients required only 1 mg of the drug to expel the fetus successfully. The mean time from the first injection of 15-Me-PGF2alpha to the expulsion of the fetus was 5.25 hours; one-half of the patients aborted in less than 4 hours. The placenta was expelled spontaneously in 15 patients, removed manually from the vagina in 18, and removed by sponge forceps in 3. Two abortions were incomplete and surgical intervention was required. Twenty-eight patients (74%) experienced gastrointestinal disturbances, chiefly vomiting and diarrhea. Intramuscular administration of 15-Me-PGF2alpha eliminates the need for repeated amniocentesis, and the dose may be adjusted to meet the precise requirements of the clinical situation.

Abortion, Induced↗

Outcome of expectant management of spontaneous first trimester miscarriage: observational study.

OBJECTIVES: To evaluate the uptake and outcome of expectant management of spontaneous first trimester miscarriage in an early pregnancy assessment unit. PARTICIPANTS: 1096 consecutive patients with a diagnosis of spontaneous first trimester miscarriage. METHODS: Each miscarriage was classified as complete, incomplete, missed, or anembryonic on the basis of ultrasonography. Women who needed treatment were given the choice of expectant management or surgical evacuation of retained products of conception under general anaesthesia. Women undergoing expectant management were checked a few days after transvaginal bleeding had stopped, or they were monitored at weekly intervals for four weeks. MAIN OUTCOME MEASURES: A complete miscarriage (absence of transvaginal bleeding and endometrial thickness <15 mm), the number of women completing their miscarriage within each week of management, and complications (excessive pain or transvaginal bleeding necessitating hospital admission or clinical evidence of infection). RESULTS: Two patients with molar pregnancies were excluded, and 37% of the remainder (408/1094) were classified as having had a complete miscarriage. 70% (478/686) of women with retained products of conception chose expectant management; of these, 27 (6%) were lost to follow up. A successful outcome without surgical intervention was seen in 81% of cases (367/451). The rate of spontaneous completion was 91% (201/221) for those cases classified as incomplete miscarriage, 76% (105/138) for missed miscarriage, and 66% (61/92) for anembryonic pregnancy. 70% of women completed their miscarriage within 14 days of classification (84% for incomplete miscarriage and 52% for missed miscarriage and anembryonic pregnancy). CONCLUSIONS: Most women with retained products of conception chose expectant management. Ultrasonography can be used to advise patients on the likelihood that their miscarriage will complete spontaneously within a given time.

Abortion, Incomplete↗

Expectant management of incomplete, spontaneous first-trimester miscarriage: outcome according to initial ultrasound criteria and value of follow-up visits.

OBJECTIVES: To assess whether the presence of a gestational sac or the width of the endometrium, can be used to predict the outcome of expectant management for an incomplete, first-trimester miscarriage, and to determine an appropriate schedule for follow-up visits. SUBJECTS: Consecutive women with a spontaneous miscarriage, who were attending an early pregnancy assessment unit. METHODS: Transvaginal ultrasonography was used at the first visit to identify those women with an incomplete miscarriage--defined as the presence of heterogeneous products of conception within the uterus and distinguishable from a missed miscarriage or an anembryonic pregnancy. The sonographic end-points were the presence of a gestational sac or the thickness of the endometrium. All subjects were offered the choice of surgical evacuation of the uterus under general anesthesia or expectant management with a follow-up visit within a few days of the cessation of transvaginal bleeding, or weekly monitoring for 4-5 weeks. The main outcome measures were the number of women with a complete miscarriage (defined as the absence of transvaginal bleeding and an endometrial thickness of < 15 mm without surgical intervention) and the proportion of women completing their miscarriage within each week of management. RESULTS: Of the 312 women who participated, 234 (75%) chose expectant management; of these 13 were lost to follow-up leaving data from 221 for analysis. Two-hundred and one (91%) completed their miscarriage without intervention; the mean time from diagnosis to completion was 9 (range, 1-32) days. By the end of week 2, 184 women (83%) had miscarried. There was no statistically significant relationship between the initial presence of a gestational sac or endometrial thickness, and the success rate of expectant management. The odds of a woman completing a miscarriage spontaneously were 1 : 1 for week 1, 2 : 1 for week 2, 1 : 2 for week 3, and 1 : 5 for week 4. Twenty women had surgical treatment (19 elective with no serious prior complications, one emergency who was admitted to the accident and emergency department on day 21 of management). There were eight elective operations during week 1, and 11 over the following 3 weeks. CONCLUSIONS: Most women with an incomplete, spontaneous miscarriage chose expectant management and had a successful outcome. Neither the presence of a gestational sac, nor the endometrial thickness at diagnosis can be used to predict the likelihood of management failure. The current schedule of regular routine follow-up visits could be safely reduced to one or two fortnightly visits as appropriate, provided that patients have ready access to clinical advice by telephone.

Abortion, Incomplete↗

A new abortion technique: intravaginal and intramuscular prostaglandin.

The 15-methyl analog of prostaglandin F2 alpha (15-ME-PGF2 alpha), administered in a 3-mg dose via a single vaginal suppository and supplemented at 24 hours by intramuscular injection(s) of 250 micrograms, successfully induced abortion in 80 of 81 patients in the midtrimester of pregnancy. The mean abortion time was 19.6 hours. Two thirds of the patients aborted after treatment with the suppository alone in a mean time of 14.6 hours; the remaining 27 patients required intramuscular injections of 15-ME-PGF2 alpha to effect expulsion of the products of conception. Twenty-six of these 27 patients subsequently aborted in a mean total abortion time of 29.6 hours. Fifty-eight patients aborted within 24 hours of the initial prostaglandin administration, and 78 aborted by 36 hours. Parity and length of gestation did not significantly affect abortion time in this series, although the mean abortion time for parous patients and patients with gestations earlier than 17 weeks tended to be somewhat shorter than that of nulliparous patients and those with more advanced gestations. The placenta was spontaneously expelled in the majority of patients. Abortion was incomplete in 3 patients and required curettage. Uterine activity, as measured via an intraamniotic catheter in 6 patients, developed very gradually with the suppository, peaking at 3 hours after insertion, and was characterized by regular contractions with low intrauterine baseline tonus. The gastrointestinal side effects that occurred in 59% of patients who received the suppository were also most frequently observed at 3 hours after administration. In contrast the gastrointestinal disturbances elicited by intramuscular injections of the analog immediately followed the administration.

Abortion, Induced↗

[Continuous extra-amniotic intracavitary application of prostaglandin F2 alpha for medicamentous induction of labour in high-risk cases of pregnancy interruption].

Reported in the paper is continuous extra-amniotic application of Prostaglandin F2 alpha (PG F2 alpha) to 70 juvenile primigravidae for termination of pregnancy. Successful priming was achieved in 54 patients after three and a half hours of induction, following administration of an average induction dose of 3 mg PG F2 alpha. Induced abortion was "incomplete or retained" and, therefore, stopped in 16 cases. An account is given of advantages of the above approach over intermittent intra-uterine application. The technique described in this paper was found to be suitable and commendable for minimizing of side-effects and risk as well as for better and individual controllability. It has also proved to reduce the variety of contra-indications to prostaglandin induction for patients with pre-existing diseases. Continuous intracavitary induction of labour may be considered as a justified alternative to the risks implied in other techniques of interruption.

Abortion, Legal↗

Manual vacuum aspiration (MVA) in the management of first trimester pregnancy loss.

BACKGROUND: Manual vacuum aspiration is not widely used for the evacuation of retained products of conception in western Europe despite its well-proven success and safety record. Nor is there much information about its use under intravenous (systemic) analgesia or patient-controlled anaesthesia in modern settings. AIM: To evaluate the use of manual vacuum aspiration for the evacuation of retained products of conception under systemic analgesia or patient-controlled anaesthesia in the management of first trimester miscarriages. METHODS: Fifty-eight women with a diagnosis of first trimester miscarriage (42 missed and 16 incomplete miscarriages) were treated with manual vacuum aspiration under systemic analgesia or patient-controlled anaesthesia. Success rates and patient satisfaction and acceptability were recorded. RESULTS: Of the 58 women recruited, 42 underwent the procedure under systemic analgesia and 15 under patient-controlled sedation while 1 woman opted for general anaesthesia. Successful evacuation was achieved in all cases. Both analgesic methods were associated with high levels of patient satisfaction and acceptability. CONCLUSIONS: Manual vacuum aspiration is an option in the management of all first trimester pregnancy losses. Comparisons with other treatment options are indicated.

Abortion, Habitual↗

Early pregnancy termination with mifepristone and misoprostol in the United States.

BACKGROUND: Mifepristone and a prostaglandin have been used successfully to terminate pregnancy in Europe and China. We report the results of a large U.S. study of mifepristone and misoprostol in women with pregnancies of up to nine weeks' duration. METHODS: We administered 600 mg of mifepristone and then 400 microg of misoprostol two days later to 2121 women seeking termination of their pregnancies at 17 centers. The women were observed for four hours after the administration of misoprostol and returned on day 15 for final assessment. RESULTS: Two thousand fifteen women completed the final assessment. Among them, pregnancy was terminated in 762 of the 827 women pregnant for < or =49 days (92 percent), 563 of the 678 women pregnant for 50 to 56 days (83 percent), and 395 of the 510 women pregnant for 57 to 63 days (77 percent) (P<0.001). Termination occurred within 4 hours after the administration of misoprostol in 49 percent of the women and within 24 hours in 75 percent. Failures, defined as cases requiring surgical intervention for medical reasons or because the patient requested it, the abortion was incomplete, or the pregnancy was ongoing, increased with increasing duration of pregnancy. The largest increase was in failures representing ongoing pregnancy, which increased from 1 percent in the < or =49-days group to 9 percent in the 57-to-63-days group (P<0.001). Abdominal pain, nausea, vomiting, diarrhea, and vaginal bleeding also increased with advancing gestational age. Two percent of the women in the < or =49-days group, as compared with 4 percent in each of the other two groups, were hospitalized, underwent surgical interventions, and received intravenous fluids (P=0.008). CONCLUSIONS: This mifepristone-misoprostol regimen is effective in terminating pregnancies, especially in women with pregnancies of 49 days' duration or less.

Abortifacient Agents, Nonsteroidal↗

Spontaneous long-term remyelination after traumatic spinal cord injury in rats.

The capability of the central nervous system to remyelinate axons after a lesion has been well documented, even though it had been described as an abortive and incomplete process. At present there are no long-term morphometric studies to assess the spinal cord (S.C.) remyelinative capability. With the purpose to understand this phenomenon better, the S.C. of seven lesionless rats and the S.C. of 21 rats subjected to a severe weight-drop contusion injury were evaluated at 1, 2, 4, 6, and 12 months after injury. The axonal diameter and the myelination index (MI = axolemmal perimeter divided by myelinated fiber perimeter) were registered in the outer rim of the cord at T9 SC level using a transmission electron microscope and a digitizing computer system. The average myelinated fiber loss was 95.1%. One month after the SC, 64% of the surviving fibers were demyelinated while 12 months later, only 30% of the fibers had no myelin sheath. The MI in the control group was 0.72 +/- 0.07 (X +/- S.D.). In the experimental groups, the greatest demyelination was observed two months after the lesion (MI = 0.90 +/- 0.03), while the greatest myelination was observed 12 months after the injury (MI = 0.83 +/- 0.02). There was a statistical difference (p < 0.02) in MI between 2 and 12 months which means that remyelination had taken place. Remyelination was mainly achieved because of Schwann cells. The proportion of small fibers (diameter = 0.5 micron or less) considered as axon collaterals, increased from 18.45% at 1 month to 27.66% a year after the contusion. Results suggest that remyelination is not an abortive phenomenon but in fact a slow process occurring parallel to other tissue plastic phenomena, such as the emission of axon collaterals.

Animals↗

Expectant management of first-trimester miscarriage in clinical practice.

BACKGROUND: The aim of this study was to evaluate treatment efficacy and patient compliance in women with an early miscarriage managed expectantly in routine clinical practice. METHODS: During 1995-98, 263 consecutive women who sought medical attention for an ongoing or incomplete miscarriage (gestational length <99 days), and who were circulatory stable and had a gestational residue measuring 15-50 mm (anterio-posterior, A-P diameter) on ultrasound examination were invited to participate in this study. Hemoglobin (Hb), C-reactive protein (CRP), human chorionic gonadotrophin (hCG), progesterone and Rh-factor were analyzed and a questionnaire regarding the pregnancy, duration of genital bleeding and number of days of absenteeism was completed on admission and after 1 and 4 weeks. RESULTS: Expectant management was considered to be complete (vaginal ultrasound, gestational residue <15 mm after 1 week) in 83%. The patients who were managed successfully by expectant management had a smaller gestational residue (p = 0.026) and a lower mean serum progesterone level (p = 0.025) on referral than in the group of women with failed expectant management. A gynecologic infection was diagnosed in seven cases (3%) and five of the infections were in the group of women who underwent dilatation and curettage. No patient required a blood transfusion. The mean number of days of absenteeism was 3.2 days. There were no differences in Hb levels before or after treatment, number of bleeding days or absenteeism between the groups. CONCLUSIONS: Expectant management of clinically stable patients with symptoms of early miscarriage is safe, efficient and well tolerated.

Abortion, Incomplete↗

Transvaginal sonohysterography: a new aid in the diagnosis of residual trophoblastic tissue.

OBJECTIVE: The study was undertaken to evaluate the diagnostic accuracy of transvaginal sonohysterography in postabortion and postpartum patients suspected of having residual trophoblastic tissue. METHODS: Twenty two women with late postabortion and postpartum bleeding were evaluated by transvaginal sonography and transvaginal sonohysterography. The patients were prospectively divided into two groups according to the sonohysterographic findings. Women with an empty uterine cavity or with free-floating masses received conservative treatment. Those with suspected attached residual trophoblastic tissue underwent curettage. RESULTS: Sonohysterography confirmed the findings of two-dimensional sonography of an empty uterus in 8 patients; however, a free floating endometrial mass was found in 4 patients and that of an empty uterine cavity in another 2 of 14 patients suspected of having residual trophoblastic tissue by the two-dimensional ultrasound. All 14 patients who were treated conservatively ceased bleeding. The 4 patients with a free-floating mass reported ejection of a vaginal mass within 6 days of treatment. Eight patients underwent curettage. Residual trophoblastic tissue was found in all of them. CONCLUSION: Transvaginal sonohysterography is a simple and effective method for the evaluation of residual trophoblastic tissue in patients with postpartum and post-abortion bleeding. Its use may eliminate unnecessary curettage procedures.

Abortion, Incomplete↗

Endometrial color flow/image-directed Doppler imaging: negative predictive value for excluding ectopic pregnancy.

PURPOSE: Visualization of an intrauterine pregnancy with transvaginal ultrasound virtually excludes an ectopic pregnancy. However, findings that might lower patients' risk for ectopic pregnancy have not been extensively investigated. We prospectively performed transvaginal color flow/image-directed Doppler imaging of the endometrium to determine the predictive value of endometrial blood flow for excluding ectopic pregnancy. MATERIALS AND METHODS: From April 1994 to August 1995, 211 consecutive women underwent transvaginal ultrasound examination to exclude an ectopic pregnancy. Color flow/image-directed Doppler imaging of the endometrium was performed on each patient. Flow was considered to be present only if a Doppler signal could be obtained with the cursor located completely within the endometrium. All Doppler imaging parameters were optimized for each patient. Resistive indices were obtained if arterial signal was present, and receiver operator characteristic curves were constructed for RI and peak systolic velocity. Findings were correlated with surgical and pathology results. RESULTS: Of 211 total patients, there were 55 ectopic pregnancies (52 diagnosed for a sensitivity of 95%), 89 incomplete spontaneous abortions, 40 completed spontaneous abortions, and 27 intrauterine pregnancies. Of 55 ectopic pregnancies diagnosed with real time imaging, 9 had areas of endometrial blood flow (6 venous, 3 arterial), and 46 did not. Of the 156 patients that did not have an ectopic pregnancy, 107 had arterial blood flow within the endometrium, and 49 had no flow. Using only cases with arterial signal, the negative predictive value of endometrial blood flow for excluding an ectopic pregnancy was 97% (107/107 + 3). The optimal cutoff values (5% false-positive rate) for peak systolic velocity and refractive index (RI) were 15 cm/s and 0.55. CONCLUSIONS: Arterial blood flow within the endometrium lowers the risk for ectopic pregnancy even when other findings that might indicate a high risk are present. Venous flow within the endometrium does not exclude an ectopic pregnancy.

Adolescent↗

Pregnancy and offspring after adjuvant chemotherapy in breast cancer patients.

A retrospective review of 227 consecutive breast cancer patients who were 35 years of age or younger and who had been given doxorubicin-containing adjuvant chemotherapy was conducted to determine the frequency of pregnancy and its effect on the clinical course of the disease. Also, the status of the newborn was evaluated. There were 33 pregnancies in 25 patients (10 pregnancies were terminated, 2 patients had spontaneous abortions, and 19 patients gave birth to full-term offspring without fetal malformation). Two patients were still pregnant at the time of this report. The median interval between the completion of chemotherapy and pregnancy was 12 months. Eight patients who became pregnant experienced temporary amenorrhea during chemotherapy. Of the 25 patients who became pregnant, recurrent disease subsequently developed in 7 and 3 died. A patient's disease-free and overall survival status was not adversely effected by pregnancy. These data illustrate that in a sizeable fraction of patients 35 years of age or younger treated with adjuvant doxorubicin-containing therapy, ovarian function remained intact and subsequent pregnancy did not affect the disease-free or overall survival of the patients.

Abortion, Incomplete↗