Mid-trimester Pregnancy Research Articles

Stimulation of myometrial and decidual prostaglandin production by amniotic fluid from term, but not midtrimester pregnancies

The effect of amniotic fluid obtained from second trimester (16–20 wks) and term pregnancies (38–41 wks) on the production of PGE and F by human amnion, decidua and myometrium at term was determined using tissue slices incubated in vitro. Midpregnancy amniotic fluid neither inhibited nor stimulated the prostanoid production by any of the tissues. In contrast, term amniotic fluid obtained before as well as after the onset of labor markedly increased the production of both PGE and PGF in decidua and myometrium from levels in Krebs solution. The prostanoid production (PGE + PGF) in amnoin was not significantly increased but the proportion of PGF was raised during incubations in term amniotic fluid. In decidua and myometrium the increase in PGE and PGF production in term amniotic fluid was approximately 200 and 400 percent respectively, from control values in Krebs solution. We propose that the stimulatory activity in term amniotic fluid in responsible for the accelerated synthesis of prostaglandins after of membranes, which is reflected in raised PGF metabolite levels in maternal circulation. It may also be the reason for the rise in amniotic fluid prostaglandin levels around the 35th week of gestation, and perhaps for the onset of labor.

Adjunctive use of Laminaria tents for termination of early mid-trimester pregnancy with intramuscular 15(S)-15-methyl PGF2 alpha.

AbstractForty‐five patients with gestational age between 12–16 weeks treated with insertion of Laminaria tents followed 14 hours later by serial intramuscular injections of 15‐methyl PGF2 alpha had a mean abortion time of 10.49 ± 0.94 hours and percentage effectiveness of 97.78% within 20 hours. Except for one case of cervical laceration, no other complications occurred. Tents reduce the drug‐abortion interval and improve the cumulative success rate. A close relationship between degree of difficulty at removal of the tents and the mean abortion interval was noted.

Midtrimester Abortion: Techniques and Complications

Midtrimester abortion may be accomplished by a variety of techniques, alone or in combination. Comprehensive care of patients who require or request pregnancy termination in the second trimester must include careful assessment of medical and psychological conditions. Special attention needs to be paid to gestational age, and for many cases ultrasonography should be part of the evaluation. With the variety of techniques and combinations available, physicians can now individualize patient care to minimize morbidity and mortality while improving patient comfort and well being.

The Effect of Essential Fatty Acid and Specific Vitamin Suppliments on Vascular Sensitivity in the Mid-Trimesier of Human Pregnancy

Vascular sensitivity to angiotensin II was determined in the mid-trimester of pregnancy in women after taking a diet with supplemented essential fatty acids and vitamins. The essential fatty acids linoleic and dihommogammalinolenic acid were administered as evening primrose oil capsules (Efamol) for one week prior to the study. Vascular sensitivity was then determined in response to 4, 8 and 16 ng kg-1 min-1 angiotensin II. Vitamin supplements (Efavit) were given with the Efamol capsules. Seven women have been studied, and their vascular sensitivity compared with controls on normal diet. The vascular sensitivity was significantly reduced in all the patients on essential fatty acid supplements, and all values fell below the mean of the control group.

Radiographic findings in cervix uteri after prostaglandin abortion induction.

Hysterography was performed on 173 nulliparous patients following termination of midtrimester pregnancy by intra-amniotic prostaglandin F2 alpha (PGF2 alpha). In 21 hysterograms (12%) a pathologically wide internal os was found, compared with three out of one hundred routine hysterograms carried out for infertility examination. A deformed cervical canal with filling defects and synechiae was found in the hysterograms of 28 patients (16%). Only one of the 6 patients with ruptured cervix had a wide internal os. A laminaria tent was inserted more frequently into the cervix of patients whose internal os was of normal wide. The clinical picture of patients and the courses of abortion inductions did not differ in other respects in patients with normal vs. wide internal cervical os. This leads us to believed that there are two types of cervix: a rigid, hypoplastic cervix with high collagen content, which when exposed to the trauma of abortion induction leads to rupture, but not necessarily to incompetence, and a softer type of cervix, very muscular, which leads to wide internal os and incompetence.

Midtrimester pregnancy termination by intravaginal administration of prostaglandin E 2

The intravaginal administration of prostaglandin E 2 (PGE 2) in repeated doses of 20 mg was evaluated for efficacy and safety in 400 midtrimester pregnancy terminations. Patients were assigned to three treatment groups. Group A (232 patients) received PGE 2 alone, Group B (106 patients) had prior intracervical laminaria insertion, Group C (62 patients) received both laminaria and continuous intravenous oxytocin infusion. Complete abortion was achieved in 328 cases (82 per cent) and there were 13 failures (3.3 per cent). Mean instillation to abortion times was 13.0 ± 0.4 SEM hours. Differences among the treatment groups were not statistically significant but outcome was more favorable in pregnancies of 16 to 19 weeks' gestation as compared with those between 13 and 15 weeks. Gastrointestinal symptoms and temperature elevation constituted the most frequent side effects. Excessive blood loss occurred in 11 cases (2.8 per cent) and live births were encountered in 12 cases (3.0 per cent). Vaginal PGE 2 is felt to be particularly acceptable for the termination of pregnancies of 16 to 19 weeks' gestation.

Synthetic laminaria for cervical dilatation prior to vacuum aspiration in midtrimester pregnancy

Potential benefits of a synthetic tent compared to the natural laminaria japonica would be: 1) uniformly sized and shaped, 2) uniformity of dilatation characteristics, 3) assurance of sterility, 4) less expense, 5) ability to control rate and amount of dilatation, and 6) ability to control shape. 20 healthy women, from 13-17 weeks gestation desiring elective abortion had 1 intracervical laminaria tent placed in the cervix after cervical dilatation was determined. The following day the tent was removed and the amount of dilatation again determined. Abortion was accomplished with dilatation and evacuation; all received oral tetracycline, 250 mg 4 times/day for 4 days. The laminaria tents were highly effective: mean cervical dilatation was 1.4 mm before insertion and 12.8 mm after the tents were removed; with no apparent differences in dilatation among the 8 nulliparous patients compared to the 12 multiparous patients. Further dilatation in 11 women was accomplished with minimal pressure. Several had mild discomfort during laminaria insertion but all attempts were successful without anesthesia. The tents came out of the cervix spontaneously in only 1 patient. There were no cervical tears, false passages, uterine infections, or retained products of conception. Use of synthetic laminaria tents appears practicable for the following reasons: 1) clinically significant dilatation and softening occurred with overnight use, 2) side effects were minimal, 3) no visible tissue reaction occurred, 4) relatively short use (less than 24 hours) lessens possibilities for infection, and 5) the small dose of magnesium sulfate appears safe. Further studies are necessary to determine the incidence of complications, to research use in patients needing cervical dilatation for other purposes, to evaluate laminaria tents with other concentrations of magnesium sulfate and different amounts of compression.

Prostacyclin production during pregnancy: Comparison of production during normal pregnancy and pregnancy complicated by hypertension

We investigated prostacyclin (PGI2) biosynthesis during pregnancy by measuring urinary excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (dinor) and 15-keto-13,14-dihydro-2,3-dinor-6-keto-prostaglandin F1 alpha (15 kd dinor) with the use of specific gas chromatography-mass spectrometry assays. Nine normotensive nonpregnant women, five normotensive women in the mid-trimester of pregnancy, eight normotensive women in the third trimester of pregnancy, and six women who developed hypertension during the third trimester provided 24-hour samples of urine. Normal pregnant women had a fivefold increase in urinary excretion of dinor in comparison to nonpregnant women (253 +/- 21 ng dinor/gm creatinine for controls vs. 1,224 +/- 110 and 1,127 +/- 152 for second and third trimesters) (mean +/- SEM). Pregnant subjects with hypertension had a significant (50%) reduction in urinary dinor excretion in comparison to normotensive pregnant subjects (561 +/- 105 ng dinor/gm creatinine). In subjects selected from each group, the ratio of dinor to 15 kd dinor remained constant. We conclude that PGI2 biosynthesis is increased during normal pregnancy, and that this increase is less in pregnancy-induced hypertension. This raises the possibility that PGI2 helps mediate hemodynamic changes during normal pregnancy, and that a relative decrease in production might be related to the pathogenesis of pregnancy-induced hypertension.

The abortifacient effect of 16,16-dimethyl-trans-δ 2-PGE 1 methyl ester, a new prostaglandin analogue, on mid-trimester pregnancies and long-term follow-up observations

The present clinical trials revealed that 16,16-Dimethyl-trans-δ 2-PGE 1 methyl ester in the form of vaginal suppositories is highly effective in inducing mid-trimester termination of pregnancies. It also showed that prior treatment with laminaria and metreurynter may enhance the success rate while reducing the incidence and severity of side effects. It is easy and safe to use clinically, with minimal side effects, and in our series, revealed no deleterious effects on ensuing reproductive physiology. However, the definite mechanism involved in the action of this new analogue to cause myometrial contractions is still not completely understood, and requires further intensive investigation.

Prostaglandin E2 attenuates the pressor response to angiotensin II in pregnant subjects but not in nonpregnant subjects

The effect of prostaglandin E2 (PGE2), 5 microgram/min-1, on the pressor response to exogenous angiotensin II (AII) has been examined in 22 women in second-trimester pregnancy and in 10 nonpregnant control subjects. PGE2 diminished the diastolic pressor response in both groups without altering basal blood pressure. This effect was significant in the pregnant group, and not significant in the nonpregnant patients. The effect was achieved by a significant increase in threshold to AII, rather than an alteration in the slope of the dose-response curve. Five pregnant patients who were given two identical infusion regimes of AII without PGE2 showed no diminution of response. The effect of PGE2 was greatest in the pregnant women who showed greatest initial sensitivity to AII, perhaps suggesting a relative deficiency of E series prostaglandins in some women by midtrimester pregnancy.

Hormonal profile during termination of midtrimester pregnancy by extraovular instillation of saline: Plasma levels of prostaglandins, progesterone and human chorionic gonadotropin

Midtrimester abortion was initiated for psychosocial reasons in 5 patients, and premature delivery in 2 patients with intrauterine fetal death using a new method for termination of pregnancy — the instillation of normal saline through the cervical canal into the extraovular space. Blood levels of 15-keto-13,14 dihydro-prostaglandin F 2 α (PGF 2 α -M) progesterone (P) and Human Chorionic Gonadotropin (HCG) were determined from the start of the procedure up to the expulsion of the fetus at frequent intervals in the peripheral circulation of these patients, by highly sensitive and specific RIA procedures. Following saline instillation and initiation of contractions, the concentration of PGF 2 α -M) increased significantly, reaching peak values either shortly before or at the time of delivery. This rise was associated with a significant decrease of P levels. Levels of HCG were variable. The possible significance of these results is discussed.

Plasma concentrations of oestrone, oestradiol, oestriol and progesterone during mechanical stretch-induced abortion at mid-trimester.

Plasma levels of unconjugated oestrone, oestradiol, oestriol and progesterone were serially studied in six uncomplicated patients in the mid-trimester of pregnancy before and during abortion induced by purely mechanical stretching of the uterus by laminaria and rubber balloon. Variability of these hormonal levels among patients was significant before the treatment. In four cases where the fetus was aborted alive, the plasma value of these hormones remained at a high level during the treatment with the exception of oestriol level in one case. In two early mid-trimester cases the fetus died during the treatment and plasma oestriol dropped significantly, while the level of the other hormones remained raised until fetal delivery. In these two cases the apparent onset of labour was noted before fetal death. It was concluded that the onset and progress of labour by mechanical stretching of the uterus is probably unrelated to the steroid hormones estimated in the present study.

Uterine activity and blood flow in response to sulprostone during midtrimester pregnancy termination.

During hysterotomy sulprostone was infused into nine patients at a rate of 5 μg/min. The appearance of the uterus changed in 15 min to white or dark blue. There was a simultaneous rise in intrauterine resting pressure (‘tone’). The use of sulprostone in postpartum haemorrhage is discussed.

Prophylaxis against prostaglandin-induced gastrointestinal side effects

Prostaglandin F 2α was administered by intravenous drip in 130 patients with missed, incomplete inevitable and septic abortion, intrauterine death and vesicular mole and for therapeutic termination of midtrimester pregnancies. In 84 patients (control group), no prophylactic antiemetic or antidiarrheal drugs were administered, while in 46 patients (study group), an antiemetic (prochlorperazine) and an antidiarrheal (diphenoxylate hydrochloride with atropine sulfate) drug were administered prophylactically before and during prostaglandin infusion. The incidence in vomiting and diarrhea was statistically much less in the study group ( P < 0.0005 for vomiting and P < 0.005 for diarrhea). There was no statistically significant difference in the success rate of prostaglandin induction in the two groups (P > 0.05).

Phosphoenolpyruvate carboxykinase activity in human amniotic fluid

Amniotic fluid samples obtained from normal pregnancies during gestation were used to quantitate the levels of phosphoenolpyruvate carboxykinase (PEPCK) activity. It is concluded that: (1) PEPCK activity was highest in the amniotic fluid cells of midtrimester pregnancies as compared to those of pregnancies close to term; (2) the activity of PEPCK seen in the amniotic fluid supernatant was about one fourth to one half of that seen in the amniotic cells; (3) the amniotic fluid supernatant PEPCK activity fluctuated very little during the entire gestation.

Origin of amniotic fluid cells in mid-trimester pregnancies.

Amniotic fluid cells provide important information about the fetus. Studies of the surface ultrastructure of such cells identified four cell populations in mid-gestational fluids. A parallel study of tissue surfaces in contact with or communicating with the amniotic fluid showed that some tissues made no contribution to the cell populations, while others contributed extensively. Two principal cell shedding mechanisms were found in mid-trimester--exfoliation of whole cells and detachment of cellular fragments. The latter mechanism was observed from skin and umbilical cords during a limited period in mid-pregnancy. The majority of cells were derived from exfoliation of squamous epithelia.

Dilation and evacuation: A preferred method of midtrimester abortion

A comparison between two methods of therapeutic termination of midtrimester pregnancies was perormed. Twenty-nine patients at 13 to 16 weeks' gestation underwent dilation and evacuation (D and E). A second group, of 29 patients at 16 to 19 weeks' gestation underwent therapeutic abortion by prostaglandin F2α instillation. There was a significantly lower complication rate (6.9% versus 55%) and a shorter hospital stay of 1 full day in the D and E group. Also, the blood loss was not significantly greater in the D and E group.

Termination of midtrimester pregnancies induced by hypertonic saline and prostaglandin F2 alpha 116 consecutive cases.

In 116 patients, abortion was induced in midtrimester by intra-amniotic administration of 20% hypertonic saline and 25 mg prostaglandin F2 alpha. Within 60 hours 113 aborted (success rate 97.4%). Of these 68.1% had aborted within 24 hours and 92.9% within 48 hours. Thirteen patients who had not aborted within 24 or 48 hours were treated with oxytocin drip. It is concluded that the combination studied is an effective abortifacient in midtrimester and that the injection-abortion time is reasonable, the great majority aborting within 48 hours. No live fetuses were delivered, and the complication rate was acceptable.

Use of intramuscular prostaglandin for failure of mid-trimester abortion by another method

Eight investigators, using a common protocol, studied the use of intramuscular (15S)-15-methyl prostaglandin F2α to abort midtrimester pregnancies which had failed treatment by other methods in 398 cases. Results of treatment of 3 subgroups, defined by reason for primary treatment failure, are presented. The combined efficacy rate was 96.2% with 79.6% of the abortions being complete. The mean time from starting intramuscular therapy to successful abortion was 7.35 hours. The incidence of gastrointestinal side-effects was lower than that previously reported for systemically administered prostaglandins. Serious complications were not appreciably different from those reported for commonly used methods of second trimester abortion except for a slightly higher incidence of excessive bleeding requiring blood replacement. Advantages of this method over currently used methods of treating failures of primary attempts to induce midtrimester abortion by pharmacologie means are discussed.

Evidence for relaxin in corpora lutea of late pregnant cows.

Relaxin was isolated from corpora lutea of third trimester pregnant cows. Fractions having relaxin activity eluted in the 6000 and 1400 molecular weight ranges when chromatographed on Bio-Gel P-10. Both fractions were shown to inhibit spontaneous contractions of the mouse uterus, and the 6000 molecular weight fraction promoted formation of the mouse interpubic ligament. Agar diffusion studies with an antiserum to purified porcine relaxin showed a continuous precipitin line with no spurring between the two bovine relaxin fractions and NIHR-P1 porcine relaxin standard. Electrofocusing of the 6000 molecular weight fraction demonstrated three fractions which were capable of inhibiting contractions of the mouse uterus and which cross-reacted with porcine relaxin antiserum. The isoelectric points of these three fractions were 8.8, 10.1, and 11.5. Large luteal cells in corpora lutea from cows in the midtrimester of pregnancy were detected that gave a positive stain for relaxin with the immunoperoxidase method.