M. Thiery

INCREASED MONOZYGOTIC TWINNING RATE AFTER OVULATION INDUCTION

Multiple births after artificial induction of ovulation (AIO) are usually considered to be due to fertilisation of multiple ova. In the East Flanders Prospective Twin Study between 1978 and 1985 the frequency of zygotic splitting after AIO (1.2%) was significantly higher than the expected frequency (0.45%) among spontaneous twins and triplets. Moreover, after AIO the frequency of zygotic division was significantly higher in triplets than in twins. AIO seems to be the first identified biological mechanism influencing the monozygotic twinning rate.

Results of Double-blind, Multicentre Study with Ritodrine in Premature Labour

A double-blind placebo-controlled multicentre study with ritodrine, a β-mimetic uterine relaxant, has been performed in 91 patients in premature labour. All patients were treated according to a fixed dosage scheme consisting of an intravenous infusion followed by oral tablets for a total of seven days. Ritodrine arrested premature labour in 80%, the placebo in 48% of the patients (P=0·02). This short treatment, however, was usually not sufficient to prolong gestation till term. Apart from a slight to moderate rise in maternal heart rate and a slight rise in systolic blood pressure, ritodrine did not give rise to any maternal or fetal side effects. The problems of patient selection and of evaluation of the results are discussed.

The value of twin surveys in the study of malformations

Congenital malformations have been investigated in a consecutive series of 445 monozygotic twin pairs coming from two twin surveys numbering 1,424 pairs. Concordant malformations were found in 6 pairs, discordant in 20 pairs. The significance of these findings is briefly discussed. The methodology of the prospective twin studies is described. The diagnosis of zygosity is based on sex, structure of placental membranes, blood groups and enzyme systems of the blood and placenta.

Zygosity determination in newborn twins using DNA variants.

A prerequisite for the optimal use of the twin method in human genetics is an accurate determination of the zygosity at birth. This diagnosis is sometimes hampered by the lack of available specific markers. We report here the use of DNA variants (restriction fragment length polymorphisms) as genetic markers for zygosity determination. We have analysed the placental DNA of 22 twin pairs with known zygosity on Southern blots by hybridisation with polymorphic human DNA probes. We looked at six different polymorphic sites using four restriction enzymes and six DNA probes. Among 10 dizygotic (DZ) pairs, only one was not demonstrably different and seven had at least two discordances. Within each of the 12 monozygotic (MZ) pairs there was complete concordance. Thus, nine of 10 dizygotic and 12 of 12 monozygotic twins were assigned their correct zygosity solely by comparison of six DNA variants. The use of these highly polymorphic DNA probes may have practical importance for antenatal diagnosis and paternity testing.

Chronic stimulation of uterine prostaglandin synthesis during cervical ripening before the onset of labor

Concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were measured in plasma of six carefully selected primigravid women with an unripe cervix at term before and at various intervals after extra-amniotic insertion of a Foley catheter with or without methylhydroxyethylcellulose (Tylose) gel. The procedure caused an acute elevation of PGFM levels within 5 min (P less than 0.025), which was maintained for at least 6 hours in the absence of uterine activation at 179 +/- 32% of the initial values (P less than 0.01). Extra-amniotic administration of Tylose gel caused an increase in PGFM levels which was both higher and more prolonged (greater than 12 hours) than insertion of a Foley catheter alone. The observations indicate that cervical ripening without concomitant uterine activation is associated with an increase in PGFM levels. They also demonstrate that prolonged activation of (intra) uterine prostaglandin synthesis may occur several hours before the onset of labor-like uterine activity. A chance finding further suggests that spontaneous rupture of the membranes too may be preceeded by an increase in (intra) uterine prostaglandin synthesis. In their totality these observations lend strong support to the proposition that an increase in (intra) uterine prostaglandin production is a prerequisite to rather than a consequence of the initiation of labor.

Plasma oxytocin in human pregnancy and parturition

Oxytocin concentrations were determined in serial peripheral plasma samples collected from clinically normal women during pregnancy and labor. Measurable concentrations of this hormone were detected in all maternal plasma samples during pregnancy, but there were wide differences in values between patients. Serial samples from individual patients revealed a pattern of gradual rise of oxytocin levels with advancing gestation and the increase in concentration was statistically significant. There were no significant differences in oxytocin levels at any stage of labor, with or without epidural analgesia. Oxytocin levels at the onset of the second stage did not differ statistically from those at crowning. Comparison of cross-sectional data showed no significant difference between the mean oxytocin concentration in early labor and in late pregnancy. Oxytocin surges occurred, but not in a regular pattern. Plasma oxytocin concentration did not increase after pelvic examination, sweeping of the membranes, low amniotomy or after cervical vibration. After spontaneous vaginal delivery, umbilical arterial plasma levels of oxytocin were consistently higher than plasma concentrations from the umbilical vein. The fetal arterio-venous difference was less pronounced at elective cesarean section. At spontaneous vaginal delivery, with and without epidural anesthesia, plasma levels from the umbilical artery were significantly higher than the maternal levels. After vaginal delivery, oxytocin levels in cord plasma were significantly higher than at elective abdominal delivery. Some methodological aspects with regard to blood sampling and to plasma oxytocin radioimmunoassay procedures are discussed. From the results presented it is concluded that the human fetus can be an important source of oxytocin and that neurohumoral birth reflexes described in animals do not occur systematically in man.

Metabolic effects of the triphasic oral contraceptive TrigynonR

Effects of Trigynon, a triphase low-dose oral contraceptive, containing ethinylestradiol and l-norgestrel in various proportions, on testosterone binding globulin, transcortin, thyroxine, free testosterone, free cortisol and free thyroxine as well as on plasma lipids and glucose tolerance were studied in 12 normal women treated for 3-6 months. Trigynon appears to have dominant estrogenic effects as evidenced from the increase in transport proteins and the decrease in free testosterone concentration. Plasma lipids were not significantly influenced; glucose tolerance was slightly, but not significantly decreased.

IMMEDIATE POSTPLACENTAL IUD INSERTION: THE EXPULSION PROBLEM

This paper reports an evaluation of immediate post-placental insertion of a non-copper (Lippes Loop D) and several copper-bearing IUD models (TCu200, TCu220C, MLCu375, MLCu250, Nova T-PP, DimélysR). Based on the analysis of a total of 2,646 insertions and 55,794 woman-months of experience, we conclude that placement of an IUD within ten minutes of delivery of the placenta is a valuable alternative to interval insertion, because this method is safe and effective. Effectiveness was significantly lower for the Lippes Loop D than for the T- and ML-IUD models tested, the latter showing roughly comparable pertinent event rates. Pertinent event rates for copper IUDs were influenced by the skill of the operator; age of the recipient only had a significant effect on effectiveness, whereas parity had no significant effect on pertinent event rates. The single and still unsolved problem associated with immediate postpartum insertion is the greater likelihood of expulsion compared with interval insertion, and this hazard is significantly much greater for the Loop than for the copper-bearing devices assessed. The evolution of the expulsion rates shows a constant time-relationship. This pattern makes it obvious why follow-up of recipients, at least during the first trimester following insertion, is mandatory if immediate post-placental IUD insertion is to be optimally effective.

Endocervical prostaglandin E2 gel for preinduction cervical softening

A single, endocervical application of a new commercial preparation of prostaglandin E2 (PGE2) gel, 0.5 mg of PGE2 in 2.5 ml (3 g), was evaluated for preinduction cervical softening. Safety and efficacy were assessed in a comparison with a 2.0 mg PGE2 vaginal tablet and placebo in normal nulliparous women at term, with low Bishop scores. Treatment was administered in randomized, double blind fashion. Overall success, defined as a progression in Bishop score of at least 3 points within 12 hours, was achieved in 22/40 (55%) of the gel group, 15/41 (37%) in the tablet treated women, and 8/40 (20%) in those receiving placebo. Of interest was the observation that of women with very unfavorable induction features (Bishop score 0-2), the cervical gel treatment resulted in a 6/8 (75%) success rate compared with 2/13 (15%) success for the vaginal tablet and 0/17 (0%) for placebo. In as much as a very low incidence of side effects accompanied this treatment scheme, expanded multi-center testing is recommended.

EFFECT OF LONG-TERM HORMONAL CONTRACEPTION ON PLASMA LIPIDS

Serum lipid and apoprotein levels were determined in fasting women after long-term use (5-12 years) of Depo Provera, Orgametril, Ortho Novum SQ, Binordiol, Microgynon-50, and Ministat. Compared with matched controls, pure progestogens (Depo Provera and Orgametril) caused a moderate decrease of TG, HDL chol, and Apo A1, whereas estrogen-dominant oral contraceptives (Ortho Novum SQ) increased the same parameters. The effects of long-term use of hormonal contraception on lipids did not differ from those predicted from short-term (6 months) studies.