Editor's highlights

      What is new?

      Gaucher's disease, named after the French doctor who first described it in 1882, is an autosomal recessive disorder which causes lipid accumulation in leukocytes and organs including liver, spleen and brain. About 1% of people in the USA are carriers and the carrier rate among Ashkenazy Jews is about 9%. Manifestations of the disease, such as anaemia, thrombocytopaenia, organomegaly and bone diseases, can be exacerbated by pregnancy, which may also cause new complications. The management of pregnancy is reviewed on page 3 by Ganovsky-Grisaru and colleagues from Israel and Europe. Enyzme replacement treatment was introduced in the early 1990s and imiglucerase, the human recombinant form, can reduce the risk of miscarriage and complications such as intrapartum and postpartum haemorrhage. European guidelines now recommend women to consider imiglucerase treatment before and during pregnancy but many questions remain. This authoritative review presents recommendations to optimise care during and after pregnancy and to alert physicians to potential complications.
      In our second review (page 9) Schwentner and colleagues from Ulm, Germany, present a rare case of complete hydatidiform mole localised to the cervix. Only three cases of cervical hydatidiform molar pregnancy have been published. This patient initially had a miscarriage, confirmed as normal pregnancy tissue, but returned two months later with severe haemorrhage due to a perforating lesion of the cervix, shown to be a hydatidiform mole. Further curettage was successful in preserving her uterus and she has remained well. The authors think the molar pregnancy occurred de novo in a consecutive pregnancy after curettage of the missed abortion. They review molar and cervical ectopic pregnancy, and recommend careful holding of the cervix with atraumatic clamps during curettage to avoid this rare complication.

      European view

      We are delighted to publish another guideline from the French College of Gynaecologists and Obstetricians (CNGOF), this time on twin pregnancy (page 12). The rate of twin delivery has increased in many countries and in France is now 1 in 64 births. This is partly due to rising maternal age but 31% of twin deliveries in France in 2003 followed fertility treatment. The hazards of twin pregnancy, which include a 44% risk of preterm delivery, are the same whether the pregnancy is spontaneous and induced. For this guideline, the CNGOF appointed a committee to define questions to be put to expert authors, who analysed the English- and French-language literature and took account of guidelines published in the UK, the USA and Canada. The quality of the evidence was graded and the texts were reviewed by practitioners working in a variety of situations. Some recommendations, such as those on prevention of preterm delivery, are classified as Level A (“based on good and consistent scientific evidence”), but many useful recommendations are a Professional Consensus – e.g. that chorionicity should be diagnosed as early as possible and that current data do not justify setting up “twin clinics” in France. The guideline is admirably concise and we believe it will be useful to clinicians everywhere.

      Obstetrics and maternal–fetal medicine

      Fetal blood sampling (FBS) is widely regarded as a necessary support to intrapartum fetal monitoring by cardiotocography (CTG) but is not systematically recommended with monitoring by ST segment analysis (STAN) of the fetal electrocardiogram. Doret and colleagues from Lyon, France, point out on page 35 that FBS has not been used in their department for many years, and they report a prospective study of 3112 consecutive high-risk women monitored by STAN over a 77-month period. The caesarean section rate for suspected fetal distress was 9.5% and no cases of neonatal encephalopathy or perinatal death occurred. There were 14 cases of fetal metabolic acidosis, however, and in 11 of these STAN guidelines had not been followed. The authors conclude that their study supports STAN usage without FBS support but warns of the consequences of guideline violations.
      Over the past 20 years the first choice in the UK for instrumental delivery has shifted from forceps to vacuum. The failure rate of the vacuum, however, may be as high as 20–30% and delivery may need to be completed with forceps. The consequences of sequential instrument use are causing increasing concern, and on page 41 Murphy and colleagues from Dublin and the UK report a study of the risk factors and maternal and neonatal morbidity. The authors studied 1360 primiparous women delivered in two British hospitals. Risk factors for sequential instrument use were fetal malposition and large neonatal head circumference, but not maternal obesity or grade of operator. Sequential instrument use caused greater maternal and neonatal morbidity than the use of forceps alone. The authors comment that obstetricians need training in the appropriate selection and use of instruments.
      Nausea and vomiting are common in early pregnancy but hyperemesis gravidarum (HG) occurs in less than 3% of pregnancies. Nevertheless HG is the most common cause of hospitalization in early pregnancy and has been found to be associated with subsequent low birth weight. This association may be due to confounding, however, as HG is more frequent among young primiparous women. On page 56 Roseboom and colleagues from Amsterdam report a study of 2190 women with HG in the Netherlands Perinatal Registry in 2000–2006. Compared to women without HG, these women were more likely to be primparous, of low socio-economic status, of non-Western descent and substance abusers, and to have conceived through assisted reproductive techniques. Pre-existing disease (including psychiatric disease) and pregnancy complications (such as hypertension) were more common in this group. The authors conclude that these factors largely explain the adverse pregnancy outcomes, but they stress the need for studies to assess the long-term consequences of HG.

      Reproductive medicine and endocrinology

      The secretory phase of the endometrial cycle was first described many years ago but the functions of the secretions remain unclear. They are presumably important for implantation. One of them is glycodelin (PP14), which can be measured in plasma, where its levels increase in the second half of the cycle. Bentin-Ley and colleagues from Copenhagen (page 60) measured glycodelin in endometrial flushing fluid at days one and seven after the LH peak, in 21 fertile and 75 infertile women. Levels at day one, compared to normal women, were higher in infertile women with abnormal fallopian tubes. Among women with unexplained infertility, day one levels were higher among those who failed to conceive after subsequent IVF, but the authors conclude that glycodelin is not a useful predictor of subsequent pregnancy.
      Insulin resistance is a key feature of polycystic ovary syndrome (PCOS), and insulin sensitizing agents such as metformin are used to treat PCOS. Metformin reduces fasting insulin levels and affects serum testosterone but these effects are greater in non-obese than obese women. Yasmin and colleagues from Leeds, UK, hypthesised that this may be due to inadequate dosing in women with higher BMI, and on page 67 they report a study of dose escalation. Forty women were divided into four groups depending on their BMI, and treated with increasing doses of metformin over a six-month period. The authors found a trend towards lower fasting insulin in women with BMI > 35, but there was no definite benefit from higher doses.

      Gynaecology and gynaecological oncology

      Premenstrual syndrome is a widely recognized but poorly defined condition. One question is whether it has different effects in women of different cultures. On page 72 Duenas and colleagues report a nationwide survey of Spanish women aged 15–49, in which 2108 women were interviewed at home and completed a premenstrual symptoms screening tool. The authors found that during the previous year, 73.7% had had premenstrual symptoms, which amounted to a moderate or severe premenstrual syndrome (PMS) in 8.9% of cases – a lower proportion than in some surveys in other countries. The severest form, premenstrual dysphoric disorder (PMDD), as defined by the standard screening tool, was seen in 1.1% – a similar proportion to that found in other Western countries. This means, say the authors, that in Spain 133,340 women suffer from PMDD and 772,487 from moderate or severe PMS which significantly impairs their daily activities.
      Laparoscopic radical hysterectomy (LRH) for early cervical cancer still seems an innovative procedure but it was first described almost 20 years ago. Its feasibility and safety are well established and studies have reported no difference in outcome when compared to traditional radical abdominal hysterectomy (RAH). Long-term follow-up studies are lacking, however. On page 83 Lee and colleagues from Seoul report a retrospective study of 24 consecutive women with FIGO stage I–II cervical cancer who underwent LRH between 1992 and 2001. Cases were matched with controls undergoing RAH. Intraoperative blood loss and length of hospital stay were greater with RAH but there were no differences in operative time, pelvic lymph node count or intra-operative complications. After a median follow-up of more than 6 years there was no significant difference between the groups in the 5-year disease-free survival rate, which was over 90%. As the authors point out, an international randomized clinical trial (the LACC001 trial) is now in progress.

      Gynaecological urology

      Pelvic organ prolapse (POP) affects almost 50% of women over the age of 50, and research continues on differences between women who develop prolapse and those who do not. Obesity and previous pregnancies are not the whole story, and interest is focusing on collagen, which can be weakened by the action of matrix metalloproteinases (MMPs). On page 113 Dviri and colleagues from Beer-Sheva, Israel, report a study of tissue obtained at hysterectomy from 20 women with and 20 without POP. Biopsies of the uterosacral ligaments and vaginal mucosa were studied using immunohistochemistry to assess their content of MMP-1 and 9. The expression of both MMPs was increased in women with POP but the authors caution that further work is needed before concluding that this is a cause, rather than an effect, of prolapse.

      Letter to the Editor – Brief Communications

      Two large studies are summarized in this section. On page 120 Kokalj and colleagues from Ljubljana report on neural tube defects (NTDs) in Slovenia following a recommendation by the Public Health Service in 1993 that all women of childbearing age should take folic acid for three months before and after conception. Data on live births and abortions during a 10-year period showed that the incidence of NTDs did not fall. Using a questionnaire, the authors compared the mothers of affected pregnancies with a control group. Use of folic acid was much lower among affected mothers than controls, but even in controls more than half the women began supplementation too late in pregnancy. Folate fortification of staple foods is another option but the authors comment that this raises ethical issues.
      In the second study, Horne and colleagues from Edinburgh report on serum hGC levels in 340 women with pain and/or bleeding in early pregnancy and an inconclusive ultrasound scan. Only 57% of those with “normally rising” hCGs went on to have a normal birth, as did two women with “slowly rising” hCGs. Concern has been expressed in the UK about the management of “pregnancy of unknown location”, and these results indicate that further work is required to improve diagnosis and prediction for women presenting with pain and bleeding in early pregnancy.