Congenital myotonic dystrophy.

We describe a case of severe congenital myotonic dystrophy (CDM). A 38-year-old primigravida, who was known to suffer from mild myotonic dystrophy (DM), conceived spontaneously and booked for confinement at 11 weeks in our unit. The couple had been fully counseled about the risks of transmission of this condition to their offspring before embarking on this pregnancy. Despite being fully aware of the risks, they declined prenatal diagnosis. The pregnancy was monitored by serial ultrasound scans. The diagnosis of CDM was suspected by ultrasound markers of borderline ventriculomegaly, polyhydramnios, and reduced fetal movements. The pregnancy ended prematurely at 33 weeks in an emergency caesarean section because of severe fetal compromise. The neonate died almost immediately after birth. The genetic analysis of cord blood confirmed severe DM. This case highlights the importance of ultrasound markers for the diagnosis of CDM in the absence of definitive prenatal diagnosis.

Effect of inhibiting the sarcoplasmic reticulum on spontaneous and oxytocin-induced contractions of human myometrium.

OBJECTIVE: 1. To assess the contribution of the sarcoplasmic reticulum calcium store in the generation of uterine smooth muscle contractions; 2. to evaluate the contribution of calcium induced calcium release or ryanodine gated calcium channels to myometrial force production. DESIGN: Laboratory scientific study. METHODS: Myometrial strips were obtained from women undergoing elective prelabour caesarean section at term. These were loaded with the calcium sensitive indicator Indo-1 allowing simultaneous assessment of intracellular calcium concentrations and force production. The effect of exposing the strips to ryanodine (which abolishes calcium induced calcium release), caffeine (which activates calcium induced calcium release) and cyclopiazonic acid (which abolishes the sarcoplasmic reticulum calcium store) was examined. RESULTS: Exposure to ryanodine had no appreciable effect on either the amplitude or the duration of the myometrial calcium and force transients but did increase the frequency of contractions (139+/-5%). Caffeine did not potentiate force. Cyclopiazonic acid increased frequency, duration and amplitude of both calcium and force transients. The ability of oxytocin to provoke calcium and force transients in the absence of extracellular calcium was abolished by cyclopiazonic acid but not by ryanodine. CONCLUSIONS: These results demonstrate that calcium induced calcium release does not play a significant role in human myometrium and that no functioning role for the ryanodine receptors in human myometrial tissue could be shown. These data suggest that the sarcoplasmic reticulum may act to limit contractions and act as a calcium sink, rather than to amplify contractions.

A comparison of the contractile properties of human myometrium obtained from the upper and lower uterine segments.

This study compared the contractile characteristics of myometrium taken from upper and lower uterine segments. Biopsies were obtained from women undergoing classical caesarean section. Myometrial strips were dissected and mounted in an organ bath, and the contractions were recorded. The cross sectional area of the contractile elements within the strips was measured enabling strips of differing dimensions to be compared. There were no significant differences in the contractile rate and force production produced by myometrium from the upper and lower segments. This study demonstrated that for contractile studies, the use of lower segment is appropriate. The results fail to demonstrate any functional regionality of the human uterus in terms of contractility.

The effects of inhibiting myosin light chain kinase on contraction and calcium signalling in human and rat myometrium.

The effect of inhibiting myosin light chain kinase on contractions of human and rat myometrium has been investigated, to determine whether force can be produced independently of myosin phosphorylation. Two inhibitors were used, wortmannin and ML-9, and their effects on spontaneous, high-K-depolarization-induced and oxytocin-induced force studied. Both inhibitors reduced and then abolished uterine force, irrespective of how it was produced; this was the case for both human and rat myometrium, and pregnant and non-pregnant tissue. The effects of wortmannin on intracellular [Ca2+] and inward Ca2+ current were examined. The data showed that the reduction in force produced by wortmannin occurs without a reduction of either the Ca2+ current or [Ca2+]. It is concluded that, under normal physiological conditions, myosin light chain kinase phosphorylation of myosin is essential for uterine force production and that there is little or no role for alternative force-producing pathways.

Intracellular calcium stores and agonist-induced contractions in isolated human myometrium.

OBJECTIVE: We hypothesized that the release of calcium from intracellular stores contributes to the contractions produced by the agonists oxytocin, carbachol, and prostaglandin F(2 )(alpha ) in human myometrium. STUDY DESIGN: Strips of myometrium were obtained at cesarean section and hysterectomy. The strips were loaded with the calcium-sensitive dye Indo-1 to enable simultaneous measurement of tension and intracellular calcium levels. Agonist-induced responses in the presence and absence of extracellular calcium were studied. RESULTS: Strips of myometrium were obtained from 48 women not in labor undergoing cesarean section and 6 women not pregnant undergoing hysterectomy. An increase in intracellular calcium level after agonist stimulation invariably preceded an increase in tension. Intracellular calcium level returned to baseline before myometrial relaxation. Oxytocin, carbachol, and prostaglandin F(2)(alpha) all gave both force and intracellular calcium responses in the absence of extracellular calcium, although both these responses were only 26% to 40% of the maximal response when extracellular calcium was present. CONCLUSIONS: Release of calcium from internal stores induced by oxytocin, carbachol, and prostaglandin F(2)(alpha) may contribute to agonist-induced myometrial force production.

The evaluation of the sperm migration test as a predictor for success with intrauterine insemination.

OBJECTIVE: The objective of this study was to prospectively evaluate the sperm migration test (SMT) as a discriminator in couples undergoing intrauterine insemination (IUI). PATIENTS AND METHODS: 261 couples underwent 797 IUI treatment cycles involving gonadotropin stimulation in the three year period. All had a diagnosis of unexplained infertility. All male partners underwent a repeat standard seminal analysis and SMT prior to the female partner undergoing controlled ovarian stimulation. RESULTS: Despite apparently normal seminal analyses before referral, in 22 samples the sperm concentration, motility or morphology were abnormal (WHO criteria). Of these, 20 couples underwent 109 cycles and achieved 2 pregnancies giving a pregnancy rate of 1.8% per cycle and a cumulative pregnancy rate of 10% per couple. From the remaining couples with normal seminal analyses, 71 had an SMT <5 million/mL and 168 had an SMT >5 million/mL. The suboptimal SMT group underwent 276 cycles (3.89 cycles per couple) and achieved 18 pregnancies giving a pregnancy rate of 6.5% per cycle and a cumulative pregnancy rate of 25.4%. The normal SMT group underwent 412 cycles (2.45 cycles per couple) and achieved 60 pregnancies giving a pregnancy rate of 14.6% per cycle and a cumulative pregnancy rate of 35.7%. CONCLUSIONS: We confirm that abnormal seminal analysis leads to poor pregnancy rates with IUI. However, an SMT <5 million/mL despite normal seminal analysis (WHO criteria) also leads to significantly worse pregnancy rates. We would recommend that prior to IUI, couples are screened using the SMT.

Seminal plasma immunoglobulin concentrations in autoimmune male subfertility.

The presence of anti-sperm antibodies (ASAs) in seminal plasma is associated with infertility. They have been shown to reduce sperm motility, interfere with cervical mucus penetration and gamete interaction, and have been shown to reduce spontaneous fertilization and pregnancy rates. Although some causes can be determined, in the majority of cases the initial event causing the immune sensitisation and the reasons for the continuing antibody secretion remains unknown. Quantitative determination of total IgG, IgA and IgM within seminal plasma had not been previously reported in patients with and without specific ASAs. Semen samples from 512 men presenting with infertility were analyzed. One hundred and forty-six men (28.5%) had seminal fluid ASAs as determined by the MAR or TAT tests. The total seminal plasma IgG and IgA concentrations were significantly elevated in the ASA-positive groups compared with ASA-negative groups (IgG: 8.83 mg/100 ml vs. 7.15, P = 0.0008; and IgA: 2.88 mg/100 ml vs. 1.64, P = 0.0001). Only 19 samples showed seminal fluid IgM, and there was no difference between the ASA positive or ASA negative samples. The significance of these findings is discussed.

Fetal growth retardation and second trimester maternal serum human chorionic gonadotrophin levels.

Second trimester maternal serum human chorionic gonadotrophin (hCG) levels in women who remained normotensive but delivered an unexplained growth retarded infant were compared with those from a control group and a group of women who developed pre-eclampsia in a retrospective observational study. Our hypothesis was that the similar placental pathological changes shared by unexplained normotensive IUGR and pre-eclampsia would be reflected by elevated maternal serum hCG levels in the second trimester. Normotensive women delivering unexplained singleton growth retarded infants were identified (n=43) and their second trimester hCG levels, taken as part of antenatal screening for Down's syndrome, were obtained. These were compared with a control group of 625 women, and a group of 48 women who subsequently developed pre-eclampsia. There was no significant difference in the hCG levels expressed as multiples of the median (MOM) between the women who delivered growth retarded fetuses (median MOM 0.96) and the control group (median MOM 0.97). The levels of hCG in the women who subsequently developed pre-eclampsia were significantly higher (median MOM 1.3, P=0.008). There were no significant differences in AFP levels in the three groups; however, the trend was towards a higher level of AFP in the fetal growth retardation group. Maternal serum hCG in the second trimester does not appear to be elevated in normotensive women who later produce a growth retarded fetus, although human chorionic gonadotrophin levels are significantly higher in women who subsequently develop pre-eclampsia.

The effect of progestagens on the carotid artery pulsatility index in postmenopausal women on oestrogen replacement therapy.

Part of the cardioprotective effect of postmenopausal oestrogen replacement therapy has been attributed to arterial vasodilation. This effect is partially reversed in the uterine artery by the addition of a progestagen. This study was designed to compare the effects of the C21 progestagen, dydrogesterone and the C19 testosterone derivative, norethisterone on the carotid artery pulsatility index (PI) (thought to represent distal impedance to flow) using a randomized double blind cross-over trial. The addition of progestagen resulted in a significant increase in the carotid artery PI from a median value of 1.67 during the oestrogen only phase to 1.77 (P = 0.02) during the combined phase. This trend was seen with both dydrogesterone and norethisterone, but there was no significant difference in the size of the effect caused by either progestagen. The addition of cyclical progestagen to ERT partially antagonizes the reduction in the carotid artery PI.

Intraumbilical oxytocin for the management of retained placenta: a randomized controlled trial.

OBJECTIVE: To evaluate the ability of intraumbilical oxytocin injection as a treatment for retained placenta after vaginal delivery to reduce the incidence of manual removal and postpartum hemorrhage. METHODS: A randomized controlled trial was set up in a university and a district general hospital. We recruited 81 women with singleton pregnancies who underwent vaginal delivery and who failed to deliver the placenta after 20 minutes of active management of the third stage of labor. Study subjects were randomized to receive either 1) an intraumbilical injection of oxytocin (20 IU in 20 mL of saline); 2) an intraumbilical injection of saline (20 mL); or 3) no treatment. Outcome measures were expulsion of the placenta within 45 minutes of delivery, need for manual removal of the placenta under anesthesia, and postpartum hemorrhage (defined as a blood loss greater than 500 mL). RESULTS: Women given an intraumbilical injection of oxytocin had a significant increase in spontaneous expulsion of the placenta within 45 minutes of delivery and fewer manual removals of the placenta, compared with women without treatment (odds ratio [OR] 11.6, 99% confidence interval [CI] 1.4, 272.8; and OR 7.4, 99% CI 1.1, 86.5; respectively). When women given intraumbilical oxytocin were compared with women given only intraumbilical saline, the difference was not statistically significant (OR 6.6, 99% CI 0.9, 77.2 for spontaneous expulsion of the placenta; and OR 4.7, 99% CI 0.8, 39.5 for manual removal). There was no significant difference in the incidence of spontaneous expulsion and manual removal of the placenta between women given intraumbilical saline injection and women without treatment (OR 1.8, 99% CI 0.1, 53.9; and OR 1.6, 99% CI 0.1, 22.4; respectively). CONCLUSION: The results of our study suggest a clinically important beneficial effect of intraumbilical oxytocin injection in the management of retained placenta.

The hypo-osmotic swelling test in recurrent miscarriage.

OBJECTIVE: To determine whether there is any association between sperm membrane integrity as determined by the hypo-osmotic swelling test score and unexplained recurrent miscarriage. DESIGN: Prospective observational study. SETTING: Tertiary referral center for recurrent miscarriage. PATIENT(S): Semen samples from 20 male partners of women who had had three or more first trimester miscarriages of unexplained etiology and semen samples from 20 prospective semen donors of unknown fertility potential. MAIN OUTCOME MEASURE(S): Sperm density, sperm motility, sperm morphology, and hypoosmotic swelling test score. RESULT(S): There was no difference in the median sperm density, the mean sperm motility, or the mean sperm morphology between the two groups. However, the recurrent miscarriage group had a significantly lower hypo-osmotic swelling test score than the control group. CONCLUSION(S): The hypo-osmotic swelling test score is significantly lower in samples from men whose partners have had unexplained recurrent spontaneous abortions. With the exception of cytogenetic abnormalities in peripheral blood karyotype, this is the first study to identify a male factor component in recurrent miscarriage.

Conservative management of azoospermia following steroid abuse.

As well as athletes and competitive body builders, recreational body builders attending gymnasia are known to abuse anabolic steroids, using doses from 10- to 40-fold above physiological levels. Androgenic steroids induce hypogonadotrophic hypogonadism with associated azoospermia, leading to infertility. Little literature exists on the treatment of steroid-induced azoospermia following the cessation of abuse. We present four cases of steroid-induced azoospermia, its conservative management and eventual return of normal semen density.

Histological study of decidual spiral arteries and the presence of maternal erythrocytes in the intervillous space during the first trimester of normal human pregnancy.

During the first trimester in normal human pregnancy, endovascular trophoblast migrate along the decidual spiral arteries and invade their walls to produce physiological change. There is controversy as to whether invading trophoblast plug the arteries and prevent blood flow into the intervillous space. Using light microscopy, placental bed sections from 25 first trimester gravid hysterectomy specimens were examined. From each specimen, one section was divided into equal central and peripheral compartments. Maternal red blood cells were present in the intervillous space in all specimens, in both central and peripheral areas. In total, 232 decidual spiral arteries were found, each of those represented by several cross sections, 136 in the central area and 96 in the periphery. Seventy-nine per cent had undergone physiological change (significantly more in the centre than in the periphery), 63 per cent contained scattered endovascular trophoblast, 20 per cent had plugs of trophoblast partially occluding the vessel and 17 per cent had plugs totally filling the vessel lumen. These data confirm that in the first trimester of normal pregnancy, maternal blood enters the intervillous space, total plugging of the arterial system by trophoblast is not common, and more spiral arteries undergo physiological change in the centre than in the periphery.

Seminal plasma lactoferrin concentrations in normal and abnormal semen samples.

Although the iron-chelating protein lactoferrin is secreted by the seminal vesicles, the precise role of lactoferrin in semen is unclear. This study aimed to determine whether there is any association between seminal lactoferrin concentrations and normal and abnormal semen samples with and without leucocytospermia. Lactoferrin concentrations were measured by radial immunodiffusion of semen samples from 368 men attending a regional andrology referral center. Routine seminal analysis, including the presence of leucocytospermia, was also performed. Results showed increased seminal lactoferrin in samples showing oligospermia (13.3 mg/100 ml) and oligoasthenospermia (13.4 mg/100 ml) compared to normospermic samples (11.2 mg/100 ml). There were no significant differences in seminal lactoferrin between normospermic samples and azoospermic samples or asthenospermic samples with normal sperm density. Although there was a trend toward increased lactoferrin concentration with leucocytospermia, this was not significant. Possible causes for raised lactoferrin in association with oligospermia are discussed.

Effects of intrapartum hydrotherapy on labour related parameters.

The use of birthing pools during labour is increasing in the United Kingdom. This is without good scientific evidence of their efficacy or safety. To further investigate the value and safety of intrapartum hydrotherapy, an historical cohort study was performed in a District General Hospital in Liverpool. The study group consisted of 100 women of low obstetric risk who used the birthing pool at some stage during their labours and the control group consisted of 100 women who were matched in terms of age, parity and obstetric history but laboured and delivered in air. The main outcome measures were operative delivery rates, duration of labour, analgesic requirements, perineal trauma and Apgar scores at 1 and 5 minutes. The results showed that nulliparas who used the birthing pool had significantly reduced operative delivery rates, a shorter second stage of labour, reduced analgesic requirements and a lower incidence of perineal trauma. In multiparas there were significant reductions in analgesic requirements.

Effects of acute changes in oestrogen on muscle function of the first dorsal interosseus muscle in humans.

1. To investigate the effect of the female reproductive hormones on muscle function, patients undergoing in vitro fertilization were tested during two phases of treatment. The first was following the downregulation of pituitary gonadotrophin releasing hormone (GnRH) receptors and the second after 9 days of gonadotrophin injections. 2. Maximal strength and fatiguability of the first dorsal interosseus muscle were assessed when oestrogen and progesterone were low, and less than 2 weeks later when oestrogen production reached supraphysiological levels. 3. There were no significant changes in either strength or fatigue resistance during acute, massive fluctuations in oestrogen. These results occurred at a time when progesterone levels remained relatively low. 4. Contrary to previous work, the present results suggest that oestrogen does not affect muscle strength.

A randomized trial of 2 regimens for the administration of vaginal prostaglandins (gemeprost) for the induction of midtrimester abortion.

The most frequently used method for second trimester termination of pregnancy is administration of gemeprost (16, 16-dimethyl-trans delta 2-prostaglandin E1methyl ester) as a vaginal pessary. This provides a safe and effective method for achieving abortion. The current prescribing advice is to insert the pessaries into the posterior vaginal fornix every 3 hours. This study compares this to a 6-hourly regimen. The median abortion interval in the 6-hour group was shorter than the 3-hour group (15 versus 16 hours respectively) but the cumulative abortion rates were similar (98% in the 3-hour group and 91.8% in the 6-hour group). The 6-hour group required a significantly lower total dose of gemeprost to induce abortion. There was no difference in the rates of side-effects in the 2 groups but those receiving pessaries every 6 hours required less analgesia. This study finds no advantage in giving gemeprost every 3 hours.