High-order multiples are increasingly common as a result of assisted reproductive technologies and represent pregnancies at exceptional risk. This article discusses the antepartum management of high-order multiples, which has in general been highly individualized and poorly studied. Care for high-order multiples should include preterm birth prevention education, the frequent assessment of maternal symptoms and cervical status by a consistent provider, individualized modification of activity, attention to maternal nutrition, ultrasonography for the assessment of fetal anatomy and intra-uterine growth and anticipation of maternal complications. Interventions such as prophylactic cerclage, uterine activity monitoring, prophylactic tocolysis or hospitalization have not improved outcome when used routinely, and guidelines for selective use will be presented. Specialized care for high-order multiples should be directed at identifying congenital anomalies, maximizing fetal growth and preventing early preterm birth, the effect of which will be to improve perinatal outcome for these exceptional pregnancies.
Women frequently use a mixture of analgesics to gain relief from the distress of childbirth and antenatally require information on their effectiveness and side-effects. One such example would be the reported long-term neonatal behavioural changes following systemic opioids such as pethidine. The most frequently reported maternal effects of epidural or spinal analgesia are prolonged symptoms of headache, backache and neurological sequelae. Large retrospective studies of postpartum symptomatology have focused on correlations with regional nerve blockade rather than on other more commonly used analgesics. Post-dural puncture headache is a recognized long-term complication of epidural nerve blockade. However, prospective studies have not confirmed any causal relationship between epidural analgesia and backache and neurological complications are five times more common after childbirth itself than after regional nerve blockade. Postpartum symptomatology describes significant morbidity in the community but its relationship to analgesia in labour is still to be proved.
Gonadotrophin hormone-releasing hormone analogue (GnRHa) therapy can induce a reduction in fibroid volume by up to 50% over a period of 3 months treatment. This effect may be beneficial in selected patients, prior to open or endoscopic myomectomy, to aid the surgical procedure by improving vision because of reduced blood loss and reduced uterine artery blood flow. Symptoms of excessive menstrual bleeding, pelvic pain and dysmenorrhoea will also be controlled. Long-term administration of GnRHa requires the use of concomitant add-back therapy, the optimal combination investigated to date being an oestrogen-progestogen continuous combined preparation.
Monochorionic (MC) placentation occurs in two-thirds of monozygous twins and approximately 0.3% of all spontaneous conceptions. Vascular anastomoses within the placenta allow intertwin transfusion to occur, which is in most cases a normal event. However, imbalance in this flow may lead to the clinical sequelae observed, with acute, chronic or reverse intertwin transfusion. Acute transfusion describes the events following the death of one of an MC twin pair in utero, with an approximately 1 in 4 chance of demise or neurological damage in the co-twin. Chronic intertwin transfusion, otherwise termed feto-fetal transfusion syndrome, arises following the gradual flux of blood from one twin (the donor) to its sibling fetus (the recipient). The ensuing polyhydramnios places the pregnancy at risk of preterm amniorrhexis and/or labour, notwithstanding the specific sequelae seen in these fetuses following chronic in utero insult. Reverse transfusion describes the most bizarre form of intertwin transfusion: acardiac twinning. Retrograde perfusion of one of the twins with deoxygenated blood leads to the formation of a non-viable acardiac parasite and a 'pump twin' struggling to maintain the cardiac output required to perfuse both twins.
The potential effects of epidural analgesia on the progress and outcome of labour have been the subject of lasting controversy. Retrospective reviews indicate that epidurals are associated with longer labours and/or an increase in the incidence of instrumental or operative delivery. Similar results were obtained in non-randomized prospective studies. None of them established a causal relationship, because without randomization the selection bias cannot be ruled out. Other factors, such as premature rupture of membranes and maternal socioeconomic status, may affect the outcome of labour. It was also reported that introduction of the on-demand epidural service did not increase the primary caesarean section rate. The few prospective randomized studies are contradictory and not very reliable owing to small patient populations and high cross-over rates. There is, however, unanimity among the authors regarding the superiority of pain relief provided by epidural blocks over systemically administered opioids.
Hysterectomy provides definitive treatment for uterine fibroids. Surgery should be offered to women whose fibroids are symptomatic; it is not indicated on the basis of uterine size alone. Myomectomy is an option for those wishing to preserve uterine function. The prospects for successful pregnancy following myomectomy are encouraging, although there is a significant risk of the later recurrence of fibroids. Laparotomy remains the most appropriate surgical approach for large fibroids, although vaginal, rather than abdominal, hysterectomy may be suitable for some women whose uteri do not exceed a 12-14 week gestation size. There is some evidence that the morbidity of abdominal procedures increases with very large uteri. Uterine shrinkage with GnRH analogues may facilitate vaginal hysterectomy and be useful prior to abdominal hysterectomy or myomectomy for very large fibroids, although cost-effectiveness for its use with abdominal procedures has not been demonstrated.
Several medicines are emerging with the potential to treat symptomatic uterine fibroids. Anti-progesterone compounds seem particularly promising. These drugs have been widely used for nearly 20 years and are known to be safe; medical politics have prevented their proper investigation for uterine fibroids. In particular, the value of mifepristone, 50 mg per day for 3 months, seems particularly promising. Further investigation is clearly warranted for this medicine. Several anti-oestrogen compounds have recently become available and may also be useful for the medical treatment of symptomatic uterine fibroids. This includes the possibility of the use of selective oestrogen receptor modulators as well as the prospect of the use of pure anti-oestrogens. On a longer time frame, inhibitors of angiogenesis may be useful. These medicines would act upon the blood supply to uterine fibroids. Physicians also have an obligation to investigate scientifically any promising naturopathic treatment that appears to have possible activity for symptomatic fibroids.
Various methods of predicting preterm labour in both singleton and multiple pregnancies have been studied including risk scoring systems, home uterine activity monitoring, cervical assessment and biochemical methods. In practice, risk scoring systems for preterm delivery perform poorly. Consensus in the literature regarding the usefulness of home uterine activity monitoring is lacking and well designed randomized controlled trials are required. Transvaginal ultrasound assessment of the cervix appears to have a role to play in the prediction of preterm labour. The presence of IFN in cervicovaginal fluid in the late second and early third trimesters is an important risk factor for preterm labour in asymptomatic women with multiple pregnancies. Preterm labour may be mediated in part by inflammatory cytokines. The measurement of these inflammatory cytokines in cervical secretions may also prove helpful in the prediction of preterm labour. It is anticipated that an improved ability to predict preterm labour in both singleton and multiple pregnancies will depend on increasing understanding of the condition's pathophysiology
Endoscopic surgery is able to replace most abdominal operations in the surgical treatment of uterine leiomyomas. The use of gonadotrophin hormone-releasing hormone analogues, arterial embolization, hysteroscopy, new techniques of morcellation, laparo-vaginal gasless laparoscopy and laparoscopic mini-laparotomy have enabled the avoidance of laparotomy incisions in most patients. The previous disadvantages of laparoscopy, namely a prolonged operating time, excessive bleeding and inadequate closure, have been overcome. Case and controlled studies have demonstrated the effectiveness of endoscopy in fibroid treatment. The surgical techniques require advanced endoscopic training.
Neuraxial opioids were first used for labour analgesia in 1980 following the description of spinal cord opioid receptors in 1979. Via these receptors in the dorsal horn, opioids modulate both the visceral and the somatic pain of labour. The onset and duration of action of the individual opioid are determined primarily by its relative lipid solubility. Neuraxial opioids have a local anaesthetic sparing effect, allowing the use of lower concentrations of both agents while maintaining analgesia. As a sole agent, intrathecal opioids can be used to provide analgesia during the first stage of labour, especially in the high-risk parturient. They also have a role in the management of perineal pain and the provision of rapid-onset analgesia. Unfortunately maternal and neonatal side-effects can occur, the most important being respiratory depression.
Preterm birth is the greatest threat to the infants in a multiple pregnancy. This chapter focuses on strategies that aim to prevent preterm birth and concentrates on the evidence derived from randomized clinical trials and systematic review of randomized clinical trials. The options to avoid a multiple pregnancy are briefly considered. Interventions that aim to prolong pregnancy, including prophylactic cervical cerclage, prophylactic tocolysis, home uterine activity monitoring and hospitalization for bed rest, are critically appraised, as are interventions that aim to improve the outcome of preterm birth. Interventions that require additional evaluation are highlighted.
The pathological appearances of uterine leiomyomas at macroscopic, histological and ultrastructural levels are described and illustrated. Features useful in the differential diagnosis from other uterine spindle cell lesions are included, and an outline is given of the variable features found in different studies of the effects of gonadotrophin hormone releasing hormone analogues on uterine leiomyomas.
Numerous case-control, cohort studies, case reports and reviews have been published during the last 5 years regarding the association between infertility and induction of ovulation and epithelial ovarian cancer. Despite this amount of published material, final conclusions regarding direct linkage between these different aspects of infertility and ovarian cancer, as well as any data relating to a putative pathogenetic mechanism, cannot be drawn. In this review we summarize the available data as well as update a previous review by Shoham published in 1994. We outline some of the information that has become available from basic research which may help to direct investigators to suitable clinical research models that may eventually serve to clarify this enigma. Finally we share ideas that focus on specific high-risk cohorts.
The rationale of ovulation induction is to achieve the development of a single follicle and ultimately a singleton healthy baby. Problems faced by women with anovulatory polycystic ovary syndrome are the sensitivity of the ovary to stimulation and health issues such as obesity. This chapter will discuss medical management including strategies to lose weight, address hyperinsulinaemia with insulin-sensitizing agents, such as metformin, and outline methods of ovulation induction from the usual first-line therapy of clomiphene citrate and the subsequent use of gonadotrophin therapy in clomiphene-resistant patients. Appropriately directed surgical ovulation induction with laparoscopic ovarian diathermy appears to be as efficacious as gonadotrophin therapy but will not be discussed in the context of this chapter.
The delivery of twins presents considerable challenges to the obstetric team, particularly in terms of decision-making, technical skills required and the need to respond quickly to changing circumstances. There is a serious lack of sound evidence upon which to base decisions concerning the method of delivery of twins. The trend towards the routine use of caesarean section is not supported by evidence of improved outcome for the infants, while maternal outcome is compromised. Specific circumstances that may have a bearing on the need for caesarean section include gestational age, presentation of the twins and chorionicity/amnionicity. Caesarean section does not eliminate the chance of fetal trauma during delivery, particularly for premature twins. The techniques of twin delivery, whether vaginal or by caesarean section, require thorough preparation for all possible eventualities, and skilled teamwork. Particular attention should be paid to emotional needs during labour, birth and afterwards, of the parents of twins.
There is increasing interest in the outcomes of multiple pregnancies as their numbers rise, mainly owing to advances in fertility-enhancing techniques. In addition, the numbers of multiple births surviving the perinatal period is increasing with the increasing survival of very tiny babies. In order to investigate these outcomes or to evaluate procedures that may improve them, it is important to consider a number of methodological issues that affect the comparability of data both between and within populations. How a birth and a multiple birth are defined, data sources, whether multiple pregnancies or individual births are being counted and the identification of multiple gestations by zygosity and chorionicity will all affect the reported outcome rates. In light of this, perinatal mortality and neurodevelopmental disabilities are examined as adverse outcomes of multiple pregnancies.
Childbirth is frequently accompanied by pain. For religious, cultural and philosophical reasons many groups have sought to prevent treatment of pain. Pain may have adverse effects on the mother and fetus. The psychological effects of severe pain should not be overlooked particularly where it is associated with an adverse fetal or maternal outcome. There are a number of different forms of pain relief in labour with differing side-effects and efficacies. The controversy concerning medical management of women in labour has been used to dissuade women from requesting pain relief. This debate has encouraged the use of a patient-centred philosophy of care that encourages the patient to retain control. However, good pain relief may allow the women to retain control if administered in a sensitive manner. The ideal analgesic in labour is discussed. Recent and future developments of analgesia in childbirth are discussed with respect to this.
Labour pain is the result of many complex interactions. Although not fully determined, the pain arises from distension of the lower uterine segment and cervical dilatation. The neural mechanism of labour has some features similar to other forms of acute pain; nociceptive information is relayed in small A delta and C afferent fibres to the dorsal horn of the spinal cord, mediated by neurotransmitters; from there it may be involved in the initiation of segmental spinal reflexes or pass through the spinothalamic tract to the brain. Many factors are activated during labour which may modify the nociceptive impulse at different stages of its passage. Some of these factors act synergistically to promote anti-nociception that peaks at delivery.
Polycystic ovarian disease (PCOD) is characterized by anovulation, eventually high luteinizing hormone (LH) levels, with increased LH pulse frequency, and hyperandrogenism. As the aetiology of the disease is still unknown, gonadotrophin-releasing hormone (GnRH) antagonists, competitive inhibitors of GnRH for its receptor, are interesting tools in order to study and treat the role of increased LH levels and pulse frequency in this disease. Their administration provokes a rapid decrease in bioactive and immunoactive LH followed by a slower decrease in follicle-stimulating hormone (FSH). In patients with PCOD, the suppression of gonadotrophin secretion eradicates the symptoms of the disease as long as the treatment lasts. Several authors have suggested that increased plasma LH levels have deleterious effects on the fertility of women with PCOD. Indeed, fewer spontaneous pregnancies with more miscarriages are observed when plasma LH levels are high. Assisted reproduction techniques such as in vitro fertilization (IVF) have provided other clues to the role of the LH secretory pattern in women with PCOD. The number of oocytes retrieved, the fertilization rate and the cleavage rate are lower in PCOD patients undergoing IVF and this is inversely correlated with FSH:LH ratio. These abnormalities are corrected when endogenous secretion of LH is suppressed. On the other hand, implantation and pregnancy rates after IVF are similar to those observed in control women. New GnRH antagonists are devoid of side effects and suppress LH secretion within a few hours without a flare-up effect. This action lasts for 10-100 hours. When GnRH antagonists are associated with i.v. pulsatile GnRH, this combination both suppresses the effect of endogenous GnRH and because of the competition for GnRH receptors restores a normal frequency of LH secretion. We have studied two women with PCOD, administering first 10 mg s.c. every 72 hours for 7 days of the GnRH antagonist Nal-Glu, then adding on top i.v. pulsatile GnRH: 10 micrograms/pulse every 90 minutes for 15 days. We thus succeeded in normalizing LH secretion pattern and observed a significant decline in testosterone levels. We failed to induce appropriate ovarian response and ovulation. In conclusion, the combination of GnRH antagonist and GnRH pulsatile treatment can re-establish normal LH secretory pattern in patients with PCOD. The failure to induce ovulation with this regimen suggests the existence of an inherent ovarian defect in women with PCOD.
Multiple gestations account for 1-2% of all pregnancies but contribute disproportionately to the incidence of both perinatal loss and fetal structural abnormalities. Ultrasound examination provides essential information about screening for, and the management of, such defects, including accurate determination of chorionicity, assessment of risk, invasive testing and selective termination if appropriate.
